SERPINA1

Summary

Gene Symbol: SERPINA1
Description: serpin family A member 1
Alias: A1A, A1AT, AAT, PI1, PRO2275, alpha1AT, alpha-1-antitrypsin, alpha-1 antitrypsin, alpha-1 protease inhibitor, alpha-1-antiproteinase, alpha-1-antitrypsin null, alpha-1-antitrypsin short transcript variant 1C4, alpha-1-antitrypsin short transcript variant 1C5, protease inhibitor 1 (anti-elastase), alpha-1-antitrypsin, serine (or cysteine) proteinase inhibitor, clade A, member 1, serpin A1, serpin peptidase inhibitor clade A (alpha-1antiproteinase, antitrypsin) member 1, serpin peptidase inhibitor clade A member 1, serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 1
Species: human

Top Publications

  1. pmc Identification and DNA sequence analysis of 15 new alpha 1-antitrypsin variants, including two PI*Q0 alleles and one deficient PI*M allele
    J P Faber
    Institut für Klinische Biochemie der Universität Bonn, Germany
    Am J Hum Genet 55:1113-21. 1994
  2. pmc Linkage specific fucosylation of alpha-1-antitrypsin in liver cirrhosis and cancer patients: implications for a biomarker of hepatocellular carcinoma
    Mary Ann Comunale
    Department of Microbiology and Immunology, Drexel Institute for Biotechnology and Virus Research, Drexel University College of Medicine, Doylestown, Pennsylvania, United States of America
    PLoS ONE 5:e12419. 2010
  3. pmc Elevation of intact and proteolytic fragments of acute phase proteins constitutes the earliest systemic antiviral response in HIV-1 infection
    Holger B Kramer
    Henry Wellcome Building for Molecular Physiology, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, Oxfordshire, United Kingdom
    PLoS Pathog 6:e1000893. 2010
  4. pmc Derlin-1 is a rhomboid pseudoprotease required for the dislocation of mutant α-1 antitrypsin from the endoplasmic reticulum
    Ethan J Greenblatt
    Biophysics Program, Stanford University, Stanford, California, USA
    Nat Struct Mol Biol 18:1147-52. 2011
  5. pmc α-1 Antitrypsin regulates human neutrophil chemotaxis induced by soluble immune complexes and IL-8
    David A Bergin
    1Respiratory Research Division, Department of Medicine, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin, Ireland
    J Clin Invest 120:4236-50. 2010
  6. pmc Polymers of Z alpha1-antitrypsin co-localize with neutrophils in emphysematous alveoli and are chemotactic in vivo
    Ravi Mahadeva
    Department of Medicine, Box 157, Level 5, Addenbrookes NHS Trust, Hills Road, Cambridge CB2 2QQ, UK
    Am J Pathol 166:377-86. 2005
  7. pmc Purification from human milk of matriptase complexes with secreted serpins: mechanism for inhibition of matriptase other than HAI-1
    I Chu Tseng
    Greenebaum Cancer Ctr, Dept of Biochemistry and Molecular Biology, Univ of Maryland Baltimore, BRB 10 027, 655 W Baltimore St, Baltimore, MD 21201, USA
    Am J Physiol Cell Physiol 295:C423-31. 2008
  8. pmc HIV replication in CD4+ T lymphocytes in the presence and absence of follicular dendritic cells: inhibition of replication mediated by α-1-antitrypsin through altered IκBα ubiquitination
    Xueyuan Zhou
    Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT 84602, USA
    J Immunol 186:3148-55. 2011
  9. ncbi Alpha-1-antitrypsin deficiency: a new paradigm for hepatocellular carcinoma in genetic liver disease
    David A Rudnick
    Department of Pediatics, Washington University School of Medicine, St Louis, MO, USA
    Hepatology 42:514-21. 2005
  10. ncbi Alpha 1-antitrypsin mutations in NAFLD: high prevalence and association with altered iron metabolism but not with liver damage
    Luca Valenti
    Department of Internal Medicine, Ospedale Policlinico, Mangiagalli e Regina Elena Fondazione IRCCS, Universita di Milano, Italy
    Hepatology 44:857-64. 2006

Detail Information

Publications259 found, 100 shown here

  1. pmc Identification and DNA sequence analysis of 15 new alpha 1-antitrypsin variants, including two PI*Q0 alleles and one deficient PI*M allele
    J P Faber
    Institut für Klinische Biochemie der Universität Bonn, Germany
    Am J Hum Genet 55:1113-21. 1994
    ..The limitation of IEF compared with DNA sequence analysis, for identification of new variants, their generation by mutagenesis, and the clinical relevance of the three deficiency alleles are discussed...
  2. pmc Linkage specific fucosylation of alpha-1-antitrypsin in liver cirrhosis and cancer patients: implications for a biomarker of hepatocellular carcinoma
    Mary Ann Comunale
    Department of Microbiology and Immunology, Drexel Institute for Biotechnology and Virus Research, Drexel University College of Medicine, Doylestown, Pennsylvania, United States of America
    PLoS ONE 5:e12419. 2010
    ..One such protein is alpha-1-antitrypsin (A1AT)...
  3. pmc Elevation of intact and proteolytic fragments of acute phase proteins constitutes the earliest systemic antiviral response in HIV-1 infection
    Holger B Kramer
    Henry Wellcome Building for Molecular Physiology, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, Oxfordshire, United Kingdom
    PLoS Pathog 6:e1000893. 2010
    ..Furthermore, a proteolytic fragment of alpha-1-antitrypsin (AAT), termed virus inhibitory peptide (VIRIP), was observed in plasma coincident with viremia...
  4. pmc Derlin-1 is a rhomboid pseudoprotease required for the dislocation of mutant α-1 antitrypsin from the endoplasmic reticulum
    Ethan J Greenblatt
    Biophysics Program, Stanford University, Stanford, California, USA
    Nat Struct Mol Biol 18:1147-52. 2011
    ..These data suggest that intramembrane proteolysis and protein dislocation share unexpected mechanistic features...
  5. pmc α-1 Antitrypsin regulates human neutrophil chemotaxis induced by soluble immune complexes and IL-8
    David A Bergin
    1Respiratory Research Division, Department of Medicine, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin, Ireland
    J Clin Invest 120:4236-50. 2010
    Hereditary deficiency of the protein α-1 antitrypsin (AAT) causes a chronic lung disease in humans that is characterized by excessive mobilization of neutrophils into the lung...
  6. pmc Polymers of Z alpha1-antitrypsin co-localize with neutrophils in emphysematous alveoli and are chemotactic in vivo
    Ravi Mahadeva
    Department of Medicine, Box 157, Level 5, Addenbrookes NHS Trust, Hills Road, Cambridge CB2 2QQ, UK
    Am J Pathol 166:377-86. 2005
    ..These findings may also explain the progression of emphysema in some individuals despite alpha(1)-antitrypsin replacement therapy...
  7. pmc Purification from human milk of matriptase complexes with secreted serpins: mechanism for inhibition of matriptase other than HAI-1
    I Chu Tseng
    Greenebaum Cancer Ctr, Dept of Biochemistry and Molecular Biology, Univ of Maryland Baltimore, BRB 10 027, 655 W Baltimore St, Baltimore, MD 21201, USA
    Am J Physiol Cell Physiol 295:C423-31. 2008
    ..Identification of matriptase-serpin inhibitor complexes provides evidence for the first time that the proteolytic activity of matriptase, from those cells that express no or low levels of HAI-1, may be controlled by secreted serpins...
  8. pmc HIV replication in CD4+ T lymphocytes in the presence and absence of follicular dendritic cells: inhibition of replication mediated by α-1-antitrypsin through altered IκBα ubiquitination
    Xueyuan Zhou
    Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT 84602, USA
    J Immunol 186:3148-55. 2011
    ..Because α-1-antitrypsin (AAT) decreases HIV replication in PBMCs and monocytic cells and decreases NF-κB activity, we postulated that AAT might ..
  9. ncbi Alpha-1-antitrypsin deficiency: a new paradigm for hepatocellular carcinoma in genetic liver disease
    David A Rudnick
    Department of Pediatics, Washington University School of Medicine, St Louis, MO, USA
    Hepatology 42:514-21. 2005
    Liver disease in alpha-1-antitrypsin (alpha1AT) deficiency is caused by a gain-of-toxic function mechanism engendered by the accumulation of a mutant glycoprotein in the endoplasmic reticulum (ER)...
  10. ncbi Alpha 1-antitrypsin mutations in NAFLD: high prevalence and association with altered iron metabolism but not with liver damage
    Luca Valenti
    Department of Internal Medicine, Ospedale Policlinico, Mangiagalli e Regina Elena Fondazione IRCCS, Universita di Milano, Italy
    Hepatology 44:857-64. 2006
    ..Heterozygosity for alpha 1-antitrypsin (AAT) mutations is a cofactor of liver damage, and AAT influences inflammation and iron metabolism...
  11. doi Polymorphisms in the SERPINA1 (Alpha-1-Antitrypsin) gene are associated with severe chronic rhinosinusitis unresponsive to medical therapy
    Shaun J Kilty
    The Department of Otolaryngology, Hôpital Hôtel Dieu de Montréal, Universite de Montreal, Montreal, Quebec, Canada
    Am J Rhinol Allergy 24:e4-9. 2010
    ..Previous population studies have suggested that heterozygote status for the AAT gene (SERPINA1) is a risk factor for chronic rhinosinusitis with nasal polyposis (CRSwNP)...
  12. ncbi A 2.1 A resolution structure of an uncleaved alpha(1)-antitrypsin shows variability of the reactive center and other loops
    S Kim
    Center for Cellular Switch Protein Structure, Korea Research Institute of Bioscience and Biotechnology, Yusong, Taejon, 305 600, Korea
    J Mol Biol 306:109-19. 2001
    ..The high-resolution structure of active alpha(1)-antitrypsin also provides evidence for the existence of localized van-der-Waals strain in the central hydrophobic core...
  13. ncbi Sequence organization and matrix attachment regions of the human serine protease inhibitor gene cluster at 14q32.1
    Stephanie J Namciu
    Division of Basic Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, A2 O25, Seattle, Washington 98109 1024, USA
    Mamm Genome 15:162-78. 2004
    ..Several differences between the MAR-Wiz predictions and the results of biochemical tests were observed. The genomic organization of the serpin gene cluster is discussed...
  14. pmc Calnexin phosphorylation attenuates the release of partially misfolded alpha1-antitrypsin to the secretory pathway
    Pamela H Cameron
    Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec H3A 2B2, Canada
    J Biol Chem 284:34570-9. 2009
    ..This is the first report in which the phosphorylation of calnexin is linked to the efficiency of secretion of a cargo glycoprotein...
  15. ncbi Analysis of the two common alpha-1-antitrypsin deficiency alleles PiMS and PiMZ as modifiers of Pseudomonas aeruginosa susceptibility in cystic fibrosis
    P Meyer
    Hauner s Childrens Hospital, University of Munich, Lindwurmstrasse 4, 80337 Munich, Germany
    Clin Genet 62:325-7. 2002
    ..Proteinase-antiproteinase imbalances are common in CF and alpha-1-antitrypsin (AAT) deficiency...
  16. ncbi Alpha 1-antitrypsin deficiency alleles in cystic fibrosis lung disease
    Despina D Frangolias
    McDonald Research Laboratories iCAPTURE Centre, Division of Biochemical Diseases, Department of Pediatrics, University of British Columbia, B C Children s Hospital, Vancouver, Canada
    Am J Respir Cell Mol Biol 29:390-6. 2003
    ..Body mass index was a significant predictor of alpha1-AT levels during exacerbations. alpha1-AT genotype is not a major contributor to the variability of pulmonary disease severity in CF...
  17. ncbi Alpha 1-antitrypsin polymerization: a fluorescence correlation spectroscopic study
    Pradipta Purkayastha
    Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Biochemistry 44:2642-9. 2005
    ....
  18. ncbi Association of the PIM3 allele of the alpha-1-antitrypsin gene with chronic obstructive pulmonary disease
    J Gupta
    Institute of Genomics and Integrative Biology, Mall Road, University Campus, Delhi 110007, India
    Clin Biochem 38:489-91. 2005
    The study investigated the association of genetic polymorphism of the alpha1AT gene with COPD.
  19. ncbi Association of improved pulmonary phenotype in Irish cystic fibrosis patients with a 3' enhancer polymorphism in alpha-1-antitrypsin
    Julia M Courtney
    Respiratory Research Group, Department of Medicine, Queen s University of Belfast, Belfast, UK
    Pediatr Pulmonol 41:584-91. 2006
    ..the relationship between a polymorphism (1237 G --> A) in the 3' enhancer region of the alpha-1-antitrypsin (AAT) gene and pulmonary disease severity in 320 CF patients recruited from two independent adult referral centers in ..
  20. ncbi Estimating the risk for alpha-1 antitrypsin deficiency among COPD patients: evidence supporting targeted screening
    Frederick J de Serres
    Center for the Evaluation of Risks to Human Reproduction, National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709 2233, USA
    COPD 3:133-9. 2006
    ..The result of the present study supports the concept of targeted screening for alpha-1 antitrypsin deficiency in countries with large populations of white (Caucasian) COPD patients...
  21. doi Alpha 1 antitrypsin activity is decreased in human amnion in premature rupture of the fetal membranes
    Noriko Izumi-Yoneda
    Department of Regenerative Medicine, University of Toyama Graduate School of Medicine and Pharmaceutical Sciences, Toyama, Japan
    Mol Hum Reprod 15:49-57. 2009
    ..However, the detailed mechanism is not well understood. Alpha 1 antitrypsin (AAT) was reported to decrease in concentration in amniotic fluid obtained from patients with PPROM...
  22. doi Molecular characterization of the new defective P(brescia) alpha1-antitrypsin allele
    Daniela Medicina
    Department of Pathology, Spedali Civili University of Brescia, Italy
    Hum Mutat 30:E771-81. 2009
    ..Among the known mutations of the alpha(1)AT gene (SERPINA1) causing alpha(1)AT deficiency, a few alleles, particularly the Z allele, may also predispose adults to liver ..
  23. pmc Is lysyl oxidase-like protein-1, alpha-1 antitrypsin, and neutrophil elastase site specific in pelvic organ prolapse?
    Weng Chi Man
    Department of Obstetrics and Gynecology, Stanford University School of Medicine, 300 Pasteur Drive, HH 333, Stanford, CA 94305 5317, USA
    Int Urogynecol J Pelvic Floor Dysfunct 20:1423-9. 2009
    ..We investigated whether the expression of alpha-1 antitrypsin (ATT), neutrophil elastase (NE), and lysyl oxidase-like protein 1 (LOXL-1) vary within the vagina in subjects with pelvic organ prolapse (POP)...
  24. pmc Prevalence of genetic polymorphisms in the promoter region of the alpha-1 antitrypsin (SERPINA1) gene in chronic liver disease: a case control study
    Karin F Kok
    Department of Gastroenterology and Hepatology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    BMC Gastroenterol 10:22. 2010
    Alpha-1 antitrypsin (A1AT) deficiency, caused by the Z allele (p.E342K) and S allele (p.E264V) in the SERPINA1 gene, can induce liver and pulmonary disease...
  25. doi Ethnic differences in alpha-1 antitrypsin deficiency in the United States of America
    Frederick J de Serres
    Center for the Evaluation of Risks to Human Reproduction, National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709 2233, USA
    Ther Adv Respir Dis 4:63-70. 2010
    Our earlier publications have demonstrated that alpha-1 antitrypsin (AAT) deficiency is not a rare disorder in the United States with at least 33,728 PI*ZZ homozygote individuals at risk.
  26. doi [Heterozygous alpha-1-antitrypsin deficiency (PiMZ): risk factor in the development of primary liver carcinoma in non-cirrhotic liver?]
    S Manekeller
    Universitätsklinik Bonn, Klinik und Poliklinik für Allgemein, Viszeral, Thorax und Gefäßchirurgie, Bonn
    Z Gastroenterol 48:1211-4. 2010
    ..report on a patient with a primary hepatocellular carcinoma in a non-cirrhotic liver, in whom heterozygosity for an AAT-deficiency allele was found (PiMZ)...
  27. ncbi HIV infection is associated with reduced serum alpha-1-antitrypsin concentrations
    Courtney L Bryan
    Department of Medicine, Denver Veterans Affairs Medical Center, 1055 Clermont Street, Denver, CO 80220, USA
    Clin Invest Med 33:E384-9. 2010
    ..Alpha-1-antitrypsin (AAT), the most abundant serine protease inhibitor in the circulation, has potent anti-HIV activity in vitro, and may ..
  28. doi SERPINA1 11478G→A variant, serum α1-antitrypsin, exacerbation frequency and FEV1 decline in COPD
    Jennifer K Quint
    Academic Unit of Respiratory Medicine, University College London, London, UK
    Thorax 66:418-24. 2011
    ..It was hypothesised that patients with chronic obstructive pulmonary disease (COPD) and this mutation have accelerated lung function decline...
  29. doi Alpha-1-antitrypsin is produced by human neutrophil granulocytes and their precursors and liberated during granule exocytosis
    Stine N Clemmensen
    The Granulocyte Research Laboratory, Department of Hematology, National University Hospital, Copenhagen, Denmark
    Eur J Haematol 86:517-30. 2011
    Alpha-1-antitrypsin (A1AT) is an important inhibitor of neutrophil proteases including elastase, cathepsin G, and proteinase 3...
  30. pmc Spontaneous hepatic repopulation in transgenic mice expressing mutant human α1-antitrypsin by wild-type donor hepatocytes
    Jianqiang Ding
    Department of Medicine and Department of Genetics, Albert Einstein College of Medicine, New York, NY, USA
    J Clin Invest 121:1930-4. 2011
    ..In the classical form of the disease, inefficient secretion of a mutant α1-antitrypsin protein (AAT-Z) results in its accumulation within hepatocytes and reduced protease inhibitor activity, resulting in liver ..
  31. pmc α-1-antitrypsin gene delivery reduces inflammation, increases T-regulatory cell population size and prevents islet allograft rejection
    Galit Shahaf
    Department of Clinical Biochemistry, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva, Israel
    Mol Med 17:1000-11. 2011
    ..Future studies may use this in vivo approach to examine the structure-function characteristics of the protective activities of AAT by manipulation of the hAAT plasmid.
  32. doi Dilatation of the ascending aorta and serum alpha 1-antitrypsin level in patients with bicuspid aortic valve
    Kadriye Orta Kilickesmez
    Department of Cardiology, Istanbul University Institute of Cardiology, Haseki, Aksaray, 34350 Istanbul, Turkey
    Heart Vessels 27:391-7. 2012
    ..In this analysis, α1AT level and age were the independent predictors of aortic dilatation (p = 0.03 and p = 0.02, respectively)...
  33. doi The role of proteases, endoplasmic reticulum stress and SERPINA1 heterozygosity in lung disease and α-1 anti-trypsin deficiency
    Catherine M Greene
    Respiratory Research Division, Department of Medicine, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin 9, Ireland
    Expert Rev Respir Med 5:395-411. 2011
    ..Mutations in the AAT gene (SERPINA1) that lead to deficiency in AAT are associated with chronic obstructive pulmonary diseases...
  34. pmc The prevalence of alpha-1 antitrypsin deficiency in Ireland
    Tomas P Carroll
    Department of Medicine, Royal College of Surgeons in Ireland Education and Research Centre, Beaumont Hospital, Dublin 9, Ireland
    Respir Res 12:91. 2011
    Alpha-1 antitrypsin deficiency (AATD) results from mutations in the SERPINA1 gene and classically presents with early-onset emphysema and liver disease...
  35. doi Combinatorial effect of TIMP-1 and α1AT gene polymorphisms on development of chronic obstructive pulmonary disease
    Manish Kumar
    Institute of Genomics and Integrative Biology, University Campus, Mall Road Delhi 110007, India
    Clin Biochem 44:1067-73. 2011
    ..To study the role of α(1)AT and TIMP-1 gene polymorphisms in development of COPD...
  36. doi Polymorphisms of hemochromatosis, and alpha-1 antitrypsin genes in Egyptian HCV patients with and without hepatocellular carcinoma
    Amal F Gharib
    Medical Biochemistry Department, Faculty of Medicine, Zagazig University, Egypt
    Gene 489:98-102. 2011
    ..Our results suggested that Carriers of the D allele of H63D mutation were significantly more likely to develop HCC...
  37. pmc α1Proteinase inhibitor regulates CD4+ lymphocyte levels and is rate limiting in HIV-1 disease
    Cynthia L Bristow
    Weill Cornell Medical College, New York, New York, United States of America
    PLoS ONE 7:e31383. 2012
    ..it acts not as a proteinase, but as a receptor for α(1)proteinase inhibitor (α(1)PI, α(1)antitrypsin, SerpinA1). Binding of α(1)PI to HLE(CS) forms a motogenic complex...
  38. pmc Folding mechanism of the metastable serpin α1-antitrypsin
    Yuko Tsutsui
    Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, OH 44106, USA
    Proc Natl Acad Sci U S A 109:4467-72. 2012
    ..We propose this as the mechanism for trapping α(1)-AT in a metastable form. Additionally, this separation of timescales in the folding of different regions suggests a mechanism by which α(1)-AT avoids polymerization during folding...
  39. pmc Conformational properties of the disease-causing Z variant of α1-antitrypsin revealed by theory and experiment
    Itamar Kass
    Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia
    Biophys J 102:2856-65. 2012
    ....
  40. pmc Secretomic analysis identifies alpha-1 antitrypsin (A1AT) as a required protein in cancer cell migration, invasion, and pericellular fibronectin assembly for facilitating lung colonization of lung adenocarcinoma cells
    Ying Hua Chang
    Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University and Hospital, Tainan, Taiwan
    Mol Cell Proteomics 11:1320-39. 2012
    ..High levels of A1AT were secreted by CL1-5, and the roles of A1AT in the influence of lung adenocarcinoma metastasis were investigated...
  41. pmc Diagnostic potential of urinary α1-antitrypsin and apolipoprotein E in the detection of bladder cancer
    Virginia Urquidi
    Cancer Research Institute, MD Anderson Cancer Center Orlando, Orlando, Florida 32806, USA
    J Urol 188:2377-83. 2012
    ..Using high throughput technologies, we identified a panel of bladder cancer associated biomarkers with potential clinical usefulness. In this study we tested 4 potential biomarkers for the noninvasive detection of bladder cancer...
  42. ncbi Molecular analysis of A1AT (S and Z) and HFE (C282Y and H63D) gene mutations in Egyptian cases with HCV liver cirrhosis
    Ahmad Settin
    Manosura University Children Hospital, Mansoura, Egypt
    J Gastrointestin Liver Dis 15:131-5. 2006
    Alpha-1-antitrypsin (A1AT) S and Z deficiency alleles and hemochromatosis (HFE) mutant C282Y, H63D alleles were reported to potentially affect the liver even if present in a heterozygous state.
  43. doi Kinetic instability of the serpin Z alpha1-antitrypsin promotes aggregation
    Anja S Knaupp
    Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia
    J Mol Biol 396:375-83. 2010
    ..Kinetic analysis of the unfolding transition showed that Z alpha(1)AT unfolds at least 1.5-fold faster than the wild type. The biological implications of these data are discussed...
  44. pmc Characterization of the molecular basis of the alpha 1-antitrypsin F allele
    H Okayama
    Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892
    Am J Hum Genet 48:1154-8. 1991
    ....
  45. ncbi Acid Denaturation of alpha1-antitrypsin: characterization of a novel mechanism of serpin polymerization
    Glyn L Devlin
    Department of Biochemistry and Molecular Biology, P O Box 13D, Monash University, 3800 Australia
    J Mol Biol 324:859-70. 2002
    ..However, they more closely resemble those formed by the pathological variant M(malton). Taken together, these data describe a novel kinetic mechanism of serine proteinase inhibitor polymerization...
  46. ncbi Grp78, Grp94, and Grp170 interact with alpha1-antitrypsin mutants that are retained in the endoplasmic reticulum
    Bela Z Schmidt
    Department of Pediatrics, Univ of Pittsburgh School of Medicine, Children s Hospital of Pittsburgh, 3705 Fifth Ave, Pittsburgh, PA 15213 2583, USA
    Am J Physiol Gastrointest Liver Physiol 289:G444-55. 2005
    ..Agents that perturb the synthesis and/or activity of ER chaperones such as tunicamycin and calcium ionophore A23187, have different effects on the solubility and degradation of alpha1-AT Z as well as on its residual secretion...
  47. doi Evidence for unfolded protein response activation in monocytes from individuals with alpha-1 antitrypsin deficiency
    Tomas P Carroll
    Respiratory Research Division, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin, Ireland
    J Immunol 184:4538-46. 2010
    The hereditary disorder alpha-1 antitrypsin (AAT) deficiency results from mutations in the SERPINA1 gene and presents with emphysema in young adults and liver disease in childhood...
  48. pmc Accelerated spirometric decline in New York City firefighters with α₁-antitrypsin deficiency
    Gisela I Banauch
    Division of Pulmonary, Department of Medicine, Montefiore Medical Center, Bronx, NY, USA
    Chest 138:1116-24. 2010
    ..Antitrypsin (AAT) deficiency is a risk factor for obstructive airway disease.
  49. pmc Emphysema associated with complete absence of alpha 1- antitrypsin in serum and the homozygous inheritance [corrected] of a stop codon in an alpha 1-antitrypsin-coding exon
    K Satoh
    Pulmonary Branch, National Heart, Lung and Blood Institute, Bethesda, MD 20892
    Am J Hum Genet 42:77-83. 1988
    ..Although the consequences to the individual (i.e., emphysema) are identical to those associated with the common homozygous Z mutation, the homozygous null bellingham form of alpha 1AT deficiency has a very different genetic basis...
  50. ncbi MVarallo: a new M(Like) alpha 1-antitrypsin-deficient allele
    Pierpaolo Coni
    Sardinian Regional Center of Alpha 1 Antitripsin Deficiency, Department of Cytomorfology, Division of Pathology, University of Cagliari, Italy
    Diagn Mol Pathol 12:237-9. 2003
    ..The resulting loss of 8 bp yields, in the second exon, a 70-71 stop codon. This new Mlike variant was denominated MVarallo from the site where it was discovered...
  51. doi Impact of plasminogen activator inhibitor-1 gene polymorphisms on primary membranous nephropathy
    Cheng Hsu Chen
    Division of Nephrology, Taichung Veterans General Hospital, Taiwan
    Nephrol Dial Transplant 23:3166-73. 2008
    ..The objective of this study was to clarify the relationship between PAI-1 gene polymorphisms and the progression of MN-associated pathologies...
  52. doi Helicobacter pylori infection and short-term intake of low-dose aspirin have different effects on alpha-1 antitrypsin/alpha-1 peptidase inhibitor (alpha1-PI) levels in antral mucosa and peripheral blood
    Thomas Wex
    Department of Gastroenterology, Hepatology and Infectious Diseases, Otto von Guericke University, Magdeburg, Germany
    Scand J Gastroenterol 43:1194-201. 2008
    ....
  53. pmc Matriptase-3 is a novel phylogenetically preserved membrane-anchored serine protease with broad serpin reactivity
    Roman Szabo
    Proteases and Tissue Remodeling Unit, Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, 30 Convent Drive, Bethesda, MD 20892, USA
    Biochem J 390:231-42. 2005
    ..Our study identifies matriptase-3 as a novel biologically active TTSP of the matriptase subfamily having a unique expression pattern and post-translational regulation...
  54. ncbi Deletion 14q(q24.3 to q32.1) syndrome: significance of peculiar facial appearance in its diagnosis, and deletion mapping of Pi(alpha 1-antitrypsin)
    Y Yamamoto
    Hum Genet 74:190-2. 1986
    ..3 to q32.1) syndrome. The level of alpha 1-antitrypsin in the patient was only about half of that of his parents and controls, and the Pi locus was tentatively assigned to band 14q32.1...
  55. ncbi Blood pressure, risk of ischemic cerebrovascular and ischemic heart disease, and longevity in alpha(1)-antitrypsin deficiency: the Copenhagen City Heart Study
    Morten Dahl
    Department of Clinical Biochemistry, Herlev University Hospital, Denmark
    Circulation 107:747-52. 2003
    ....
  56. pmc Chronic obstructive pulmonary disease in alpha1-antitrypsin PI MZ heterozygotes: a meta-analysis
    C P Hersh
    Channing Laboratory, Department of Medicine, Brigham and Women s Hospital and Harcard Medical School, 181 Longwood Avenue, Boston, MA 02115, USA
    Thorax 59:843-9. 2004
    ..The risk of COPD in PI MZ heterozygous individuals is controversial...
  57. ncbi Cryptic haplotypes of SERPINA1 confer susceptibility to chronic obstructive pulmonary disease
    Sally Chappell
    Division of Clinical Chemistry, Molecular Medical Sciences, Institute of Genetics, University Hospital, Queens Medical Centre, University of Nottingham, Nottingham, United Kingdom
    Hum Mutat 27:103-9. 2006
    ..The most widely recognized candidate gene in COPD is SERPINA1, although it has been suggested that SERPINA3 may also play a role...
  58. doi SERPINA1 gene variants in individuals from the general population with reduced alpha1-antitrypsin concentrations
    Michele Zorzetto
    Center for Diagnosis of Severe Alpha1 antitrypsin Deficiency, Laboratory of Biochemistry and Genetics, Institute for Respiratory Disease and Unit of Statistics and Biometry, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Italy
    Clin Chem 54:1331-8. 2008
    ..We decided to perform an exhaustive investigation of SERPINA1 gene variants in individuals from the general population with a moderately reduced serum AAT concentration, ..
  59. pmc A null deficiency allele of alpha 1-antitrypsin, QOludwigshafen, with altered tertiary structure
    G C Frazier
    Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada
    J Clin Invest 86:1878-84. 1990
    ..A total of 13 different alpha 1AT deficiency alleles, 6 of them null alleles, have been sequenced to date...
  60. pmc The human alpha 1-antitrypsin gene is transcribed from two different promoters in macrophages and hepatocytes
    E Perlino
    European Molecular Biology Laboratory, Heidelberg, FRG
    EMBO J 6:2767-71. 1987
    ..In addition, in macrophages two distinct mRNAs are generated transcript by alternative splicing. These results suggest that alpha 1-AT gene transcription responds to two different cell-specific regulatory mechanisms...
  61. ncbi Hydrolytic inactivation of a breast carcinoma cell-derived serpin by human stromelysin-3
    D Pei
    Department of Internal Medicine, University of Michigan, Ann Arbor 48109
    J Biol Chem 269:25849-55. 1994
    ....
  62. ncbi Inhibition of HIV-1 gp160-dependent membrane fusion by a furin-directed alpha 1-antitrypsin variant
    E D Anderson
    Vollum Institute, Oregon Health Sciences University, Portland 97201
    J Biol Chem 268:24887-91. 1993
    ..The potential use of alpha 1-PDX in manipulating the activation of proproteins in a tissue- and time-specific manner is discussed...
  63. ncbi Biosynthesis of alpha1-proteinase inhibitor by human lung-derived epithelial cells
    J Cichy
    Department of Microbiology and Immunology, Institute of Molecular Biology, Jagiellonian University, 31 120 Krakow, Poland
    J Biol Chem 272:8250-5. 1997
    ....
  64. pmc Chemical chaperones mediate increased secretion of mutant alpha 1-antitrypsin (alpha 1-AT) Z: A potential pharmacological strategy for prevention of liver injury and emphysema in alpha 1-AT deficiency
    J A Burrows
    Departments of Pediatrics, Washington University School of Medicine, Division of Gastroenterology and Nutrition, Children s Hospital, St Louis, MO 63110, USA
    Proc Natl Acad Sci U S A 97:1796-801. 2000
    ....
  65. pmc Cleaved antitrypsin polymers at atomic resolution
    M A Dunstone
    The Ian Potter Foundation Protein Crystallography Laboratory, St Vincent s Institute of Medical Research, Fitzroy, Victoria, Australia
    Protein Sci 9:417-20. 2000
    ..Here, we describe the first crystallographic evidence of a beta-strand linked polymer form of alpha1-antitrypsin: the crystal structure of a cleaved alpha1-antitrypsin polymer...
  66. ncbi Oxidation of either methionine 351 or methionine 358 in alpha 1-antitrypsin causes loss of anti-neutrophil elastase activity
    C Taggart
    Pulmonary Division, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin 9, Ireland
    J Biol Chem 275:27258-65. 2000
    ..We suggest that inactivation of alpha(1)-antitrypsin by oxidation of either methionine 351 or 358 provides a mechanism for regulation of its activity at sites of inflammation...
  67. pmc Topography of a 2.0 A structure of alpha1-antitrypsin reveals targets for rational drug design to prevent conformational disease
    P R Elliott
    Department of Medicine, University of Cambridge, The Wellcome Trust Centre for Molecular Mechanisms in Disease, Cambridge Institute for Medical Research, United Kingdom
    Protein Sci 9:1274-81. 2000
    ..This structure allows us to define five cavities that are potential targets for rational drug design to develop agents that will prevent conformational transitions and ameliorate the associated disease...
  68. ncbi Chronic liver disease in heterozygous alpha1-antitrypsin deficiency PiZ
    H P Fischer
    Department of Pathology, University of Bonn, Germany
    J Hepatol 33:883-92. 2000
    ..We analyzed whether patients with this genetic defect carrying a single PiZ gene are at increased risk for developing chronic liver disease...
  69. ncbi 6-mer peptide selectively anneals to a pathogenic serpin conformation and blocks polymerization. Implications for the prevention of Z alpha(1)-antitrypsin-related cirrhosis
    Ravi Mahadeva
    Respiratory Medicine Unit, Department of Medicine, University of Cambridge, Cambridge CB2 2XY, United Kingdom
    J Biol Chem 277:6771-4. 2002
    ..Furthermore they demonstrate how a conformational disease process can be selectively inhibited with a small peptide...
  70. ncbi Change in lung function and morbidity from chronic obstructive pulmonary disease in alpha1-antitrypsin MZ heterozygotes: A longitudinal study of the general population
    Morten Dahl
    Department of Clinical Biochemistry 54M1, Herlev University Hospital, Herlev Ringvej 75, DK 2730 Herlev, Denmark
    Ann Intern Med 136:270-9. 2002
    ..A deteriorating effect of severe alpha(1)-antitrypsin deficiency (ZZ genotype) on lung function is well known, whereas the role of intermediate deficiency (MZ genotype) remains uncertain...
  71. ncbi Gene regulation of the serine proteinase inhibitors alpha1-antitrypsin and alpha1-antichymotrypsin
    Noor Kalsheker
    Division of Clinical Chemistry, School of Clinical Laboratory Sciences, University Hospital, Queen s Medical Centre, Nottingham NG7 2UH, U K
    Biochem Soc Trans 30:93-8. 2002
    ..The most abundant serpins in human plasma are alpha(1)-antitrypsin (AAT) and alpha(1)-antichymotrypsin (ACT)...
  72. ncbi Interactions causing the kinetic trap in serpin protein folding
    Hana Im
    National Creative Research Initiatives, Protein Strain Research Center, Korea Institute of Science and Technology, 39 1 Hawolgok Dong, Sungbuk Gu, Seoul 136 791, Korea
    J Biol Chem 277:46347-54. 2002
    ..Mutational analyses suggest strongly that interactions not found in the final stable form cause the kinetic trap in serpin protein folding...
  73. pmc Liver injury in alpha1-antitrypsin deficiency: an aggregated protein induces mitochondrial injury
    David H Perlmutter
    University of Pittsburgh School of Medicine, Children s Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA
    J Clin Invest 110:1579-83. 2002
  74. pmc Alpha1-antitrypsin polymerization and the serpinopathies: pathobiology and prospects for therapy
    David A Lomas
    Respiratory Medicine Unit, Department of Medicine, University of Cambridge, Cambridge Institute for Medical Research, Cambridge, United Kingdom
    J Clin Invest 110:1585-90. 2002
  75. ncbi Genetic epidemiology of alpha-1 antitrypsin deficiency in southern Europe: France, Italy, Portugal and Spain
    F J de Serres
    Laboratory of Molecular Toxicology, Environmental Toxicology Program, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709 2233, USA
    Clin Genet 63:490-509. 2003
    Alpha-1-antitrypsin deficiency (AAT deficiency) is one of the most common serious hereditary disorders in the world because it affects all major racial subgroups worldwide and there are at least 120...
  76. ncbi Canonical inhibitor-like interactions explain reactivity of alpha1-proteinase inhibitor Pittsburgh and antithrombin with proteinases
    Alexey Dementiev
    Department of Biochemistry and Molecular Genetics, College of Medicine, University of Illinois at Chicago, Chicago, Illinois 60607, USA
    J Biol Chem 278:37881-7. 2003
    ..This suggests a general, limited, canonical-like interaction between serpins and proteinases in their Michaelis complexes...
  77. ncbi HIV-1 preferentially binds receptors copatched with cell-surface elastase
    Cynthia L Bristow
    Laboratory of Cellular Physiology and Immunology, The Rockefeller University and Population Council, New York, NY 10021, USA
    Blood 102:4479-86. 2003
    ....
  78. ncbi Are polymorphic markers within the alpha-1-antitrypsin gene associated with risk of human immunodeficiency virus disease?
    Vanessa M Hayes
    Department of Urology, University of Stellenbosch, Faculty of Health Sciences, Tygerberg, South Africa
    J Infect Dis 188:1205-8. 2003
    We sought to determine whether variants of the human alpha-1-antitrypsin (AAT) gene, also known as "PI," or "SERPINA1," are associated with human immunodeficiency virus (HIV) infection in 2 African-based populations from HIV-pandemic sub-..
  79. ncbi Activation of endoplasmic reticulum-specific stress responses associated with the conformational disease Z alpha 1-antitrypsin deficiency
    Matthew W Lawless
    Respiratory Research Division, Royal College of Surgeons in Ireland, Education and Research Center, Beaumont Hospital, Dublin, Ireland
    J Immunol 172:5722-6. 2004
    ..Z alpha1-antitrypsin (A1AT) deficiency is a genetic disease associated with accumulation of misfolded A1AT in the endoplasmic reticulum (ER) ..
  80. pmc Serine protease inhibitors serpina1 and serpina3 are down-regulated in bone marrow during hematopoietic progenitor mobilization
    Ingrid G Winkler
    Haematopoietic Stem Cell Laboratory, Mater Medical Research Institute, South Brisbane, Queensland 4101, Australia
    J Exp Med 201:1077-88. 2005
    ..activity of these neutrophil serine proteases is regulated by the expression of naturally occurring inhibitors (serpina1 and serpina3) produced locally within the bone marrow...
  81. ncbi Accumulation of mutant alpha1-antitrypsin Z in the endoplasmic reticulum activates caspases-4 and -12, NFkappaB, and BAP31 but not the unfolded protein response
    Tunda Hidvegi
    Department of Pediatrics, University of Pittsburgh School of Medicine, Children s Hospital of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA
    J Biol Chem 280:39002-15. 2005
    In alpha(1)-antitrypsin (alpha1AT) deficiency, a polymerogenic mutant form of the secretory glycoprotein alpha1AT, alpha1ATZ, is retained in the endoplasmic reticulum (ER) of liver cells...
  82. ncbi Estimated numbers and prevalence of PI*S and PI*Z alleles of alpha1-antitrypsin deficiency in European countries
    I Blanco
    Div of Internal Medicine, Respiratory Diseases Branch, Hospital Valle del Nalon, 33920 Langreo, Principado de Asturias, Spain
    Eur Respir J 27:77-84. 2006
    ..A remarkable lack in number of reliable epidemiological studies and marked differences among these European countries and regions within a given country was also found...
  83. ncbi Characterization and suppression of dysfunctional human alpha1-antitrypsin variants
    Min Jung Kim
    Department of Molecular Biology, Conformational Disease Research Center, Sejong University, 98 Gunja Dong, Kwangjin gu, Seoul 143 747, Republic of Korea
    Biochem Biophys Res Commun 343:295-302. 2006
    ....
  84. ncbi Serpin A1 and CD91 as host instruments against HIV-1 infection: are extracellular antiviral peptides acting as intracellular messengers?
    Luis Fernando Congote
    Endocrine Laboratory, McGill University Health Centre, 687 avenue des pins, ouest, Montreal, H3A 1A1, Canada
    Virus Res 125:119-34. 2007
    b>Serpin A1 (alpha1-antitrypsin, alpha1-proteinase inhibitor) has been shown to be a non-cytolytic antiviral factor present in blood and effective against HIV infection...
  85. ncbi Alpha1-antitrypsin, old dog, new tricks. Alpha1-antitrypsin exerts in vitro anti-inflammatory activity in human monocytes by elevating cAMP
    Sabina M Janciauskiene
    Department of Clinical Sciences, University Hospital Malmo, Lund University, SE 20502 Malmo, Sweden
    J Biol Chem 282:8573-82. 2007
    ..Regulation of serine protease activity is considered to be the sole mechanism for the function of alpha1-antitrypsin (AAT)...
  86. doi Prevalence of common HFE and SERPINA1 mutations in patients with hepatocellular carcinoma in a Moroccan population
    Sayeh Ezzikouri
    Laboratoire de Virologie, Institut Pasteur du Maroc, Casablanca, Morocco
    Arch Med Res 39:236-41. 2008
    Hereditary hemochromatosis and SERPINA1 mutation were reported to affect liver functions...
  87. ncbi PI S and PI Z alpha-1 antitrypsin deficiency worldwide. A review of existing genetic epidemiological data
    F J de Serres
    Center for the Evaluation of Risks to Human Reproduction, Environmental Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709 2233, USA
    Monaldi Arch Chest Dis 67:184-208. 2007
    b>AAT deficiency is not a rare disease, but one of the most common congenital disorders increasing susceptibility of deficiency individuals to both lung and liver disease as well as other several adverse health effects...
  88. doi Alpha-1 antitrypsin Null mutations and severity of emphysema
    Laura Fregonese
    Department of Pulmonology, Leiden University Medical Centre, Leiden, The Netherlands
    Respir Med 102:876-84. 2008
    Alpha-1 antitrypsin (AAT) deficiency is an autosomal-codominant disorder, caused by mutations in the SERPINA1 gene on chromosome 14...
  89. pmc Alpha-1-antitrypsin is an endogenous inhibitor of proinflammatory cytokine production in whole blood
    Gregory B Pott
    Denver Veterans Affairs Medical Center, Department of Medicine, Division of Infectious Diseases, University of Colorado Denver, 12700 E 19th Ave, Aurora, CO 80045, USA
    J Leukoc Biol 85:886-95. 2009
    ..alpha-1-Antitrypsin (AAT) is the most abundant serine protease inhibitor in blood, and AAT possesses anti-inflammatory activity in vitro and ..
  90. pmc HDL antielastase activity prevents smooth muscle cell anoikis, a potential new antiatherogenic property
    Guadalupe Ortiz-Muñoz
    INSERM U698, Paris, France
    FASEB J 23:3129-39. 2009
    ..Using mass spectrometry and Western blotting, we showed the presence of alpha(1)-antitrypsin (AAT) (SERPINA1, serpin peptidase inhibitor, clade A, an elastase inhibitor) in HDL, isolated either by ultracentrifugation or by ..
  91. ncbi Genetic variants of alpha1-antitrypsin
    Parveen Salahuddin
    DISC, InterdisciplinaryBiotechnology Unit, AMU, Aligarh, 202002, India
    Curr Protein Pept Sci 11:101-17. 2010
    ..The examples of some of the null variants are QOcardiff, QOhong kong, QOgranite falls, QObellingham, QOmattawa, QObolton, and QOludwigshafen. The molecular basis of deficiency of these variants also forms the theme of this review...
  92. pmc Alpha-1-antitrypsin deficiency and smoking as risk factors for mismatch repair deficient colorectal cancer: a study from the colon cancer family registry
    Noralane M Lindor
    Department of Medical Genetics, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
    Mol Genet Metab 99:157-9. 2010
    In a previous study, alpha-1-antitrypsin (A1AT) deficiency alleles were found to be over represented among individuals with microsatellite unstable (MSI-high) colorectal cancers, and this was most significant in former or current smokers...
  93. doi Novel proteomic strategy reveal combined alpha1 antitrypsin and cathepsin D as biomarkers for colorectal cancer early screening
    Li Qi Xie
    Department of Chemistry and Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, People s Republic of China, Key Laboratory of Medical Molecular Virology, Shanghai Medical College, Fudan University, Shanghai 200032, People s Republic of China, and Affiliated Tumor Hospital of Fudan University, Shanghai 200032, People s Republic of China
    J Proteome Res 9:4701-9. 2010
    ..Two glycol-proteins, alpha1 antitrypsin (A1AT) and cathepsin D (CTSD), which play central role in proteasome regulation, were further examined due to their ..
  94. pmc Alpha1-antitrypsin deficiency carriers, serum alpha 1-antitrypsin concentration, and non-small cell lung cancer survival
    Yan Li
    Department of Respiratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing, People s Republic of China
    J Thorac Oncol 6:291-5. 2011
    ....
  95. pmc Dynamic local unfolding in the serpin α-1 antitrypsin provides a mechanism for loop insertion and polymerization
    Beena Krishnan
    Department of Biochemistry and Molecular Biology, University of Massachusetts Amherst, Amherst, Massachusetts, USA
    Nat Struct Mol Biol 18:222-6. 2011
    ..Mutations in α₁AT that cause polymerization-induced serpinopathies map to the labile region, suggesting that the evolution of serpin function required sampling of high risk conformations on a dynamic energy landscape...
  96. pmc SERPINA1 PiZ and PiS heterozygotes and lung function decline in the SAPALDIA cohort
    Gian Andri Thun
    Swiss Tropical and Public Health Institute, Basel, Switzerland
    PLoS ONE 7:e42728. 2012
    Severe alpha1-antitrypsin (AAT) deficiency is a strong risk factor for COPD. But the impact of gene variants resulting in mild or intermediate AAT deficiency on the longitudinal course of respiratory health remains controversial...
  97. pmc Cytosolic, autocrine alpha-1 proteinase inhibitor (A1PI) inhibits caspase-1 and blocks IL-1β dependent cytokine release in monocytes
    Yonggang Wang
    Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD, USA
    PLoS ONE 7:e51078. 2012
    ..These studies examine the relationship between A1PI expression in primary monocytes and monocytic cell lines, and inflammatory cytokine expression in response to inflammasome directed stimuli...
  98. ncbi Structure of a serpin-protease complex shows inhibition by deformation
    J A Huntington
    Department of Haematology, University of Cambridge, Wellcome Trust Centre for Molecular Mechanisms in Disease, Cambridge Institute for Medical Research, UK
    Nature 407:923-6. 2000
    ..It is this ability of the conformational mechanism to crush as well as inhibit proteases that provides the serpins with their selective advantage...
  99. pmc Elucidation of the molecular logic by which misfolded alpha 1-antitrypsin is preferentially selected for degradation
    Ying Wu
    Department of Pathology, Baylor College of Medicine, Houston, TX 77030 3498, USA
    Proc Natl Acad Sci U S A 100:8229-34. 2003
    ..For newly synthesized alpha1-antitrypsin (AAT), the modification of its asparagine-linked oligosaccharides by a slow-acting mannosidase partitions the misfolded ..
  100. ncbi Comprehensive glyco-proteomic analysis of human alpha1-antitrypsin and its charge isoforms
    Daniel Kolarich
    Department of Chemistry, Biochemistry Division, University of Natural Resources and Applied Life Sciences BOKU, Vienna, Austria
    Proteomics 6:3369-80. 2006
    ..Fucosylation of diantennary structures was marginal and of the core alpha1,6 type...
  101. ncbi High prevalence of alpha-1-antitrypsin heterozygosity in children with chronic liver disease
    Kathleen M Campbell
    Pediatric Liver Care Center, Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children s Hospital Medical Center, Cincinnati, OH 45229, USA
    J Pediatr Gastroenterol Nutr 44:99-103. 2007
    Alpha-1-antitrypsin (A1AT) deficiency is the most common genetic cause of liver disease in children; however, the role of polymorphic heterogeneity in the A1AT gene as a modifier of other forms of pediatric liver disease is not clear...

Research Grants62

  1. Generation of interfering RNA molecules by trans-splicing
    COLETTE COTE; Fiscal Year: 2006
    ..aims: In specific aim 1 we will develop PTMs that form novel pri-miRNAs capable of generating alpha-1 antitrypsin (AAT)-, human papillomavirus-16 (HPV16)- or TATA box binding protein (TBP)-specific miRNAs in tissue culture cells...
  2. Mice Humanized with Hepatocytes and iPS Cells from Patients with Metabolic Diseas
    Stephen C Strom; Fiscal Year: 2010
    ..While many patients with alpha-1-antitrypsin (A1AT) deficiency develop liver fibrosis/cirrhosis many times resulting in liver transplantation, the transgenic mouse ..
  3. Phase 2 Study of rAAV1-CB-hAAT for Treatment of Alpha-1 Antitrypsin Deficiency
    Jeffrey D Chulay; Fiscal Year: 2013
    ..deficiency is an inherited, genetic condition characterized by reduced serum levels of alpha-1 antitrypsin (AAT) and increased risk of developing emphysema and liver disease, which affects up to 100,000 individuals in the ..
  4. Novel Protective Antiapoptotic Action of Alpha 1-Antitrypsin In Emphysema
    Rubin M Tuder; Fiscal Year: 2011
    ..and activity of alpha-1 antritrypsin and may provide an opportunity improve our therapeutic approaches in alpha 1 antitrypsin deficiency- and smoking-induced emphysema...
  5. The Pathobiology of Airway Disease in Alpha-1 Antitrypsin Deficiency
    Michael A Campos; Fiscal Year: 2010
    ..the normal airway epithelium and airway submucosal glands (SMG) secrete significant amounts of alpha-1 antitrypsin (AAT)...
  6. Stephen R Wisniewski; Fiscal Year: 2015
    ....
  7. Characterization of human hematopoietic and endodermal progenitors derived from i
    Gustavo Mostoslavsky; Fiscal Year: 2010
    ..from individuals with the two most common inherited lung diseases: cystic fibrosis (CF) or alpha-1 antitrypsin (AAT)-related emphysema...
  8. Christian Mueller; Fiscal Year: 2016
    ..Z patients suffer from a lung disease that is due to the lack of normal antiprotease function of the wild-type AAT, and may also suffer from a liver disease, that appears to be triggered by retention of polymeric and/or aggregated ..
  9. AAT Deficiency & Liver Diseases Caused by Proteins
    Bruce Trapnell; Fiscal Year: 2006
    ..conference focuses on an important, emerging topic: the molecular pathogenesis and therapy for Alpha-1 Antitrypsin (AAT) Deficiency and other inherited metabolic disorder of protein folding...
  10. Small molecules to treat alpha-1 antitrypsin deficiency
    Chen Liu; Fiscal Year: 2006
    DESCRIPTION (provided by the applicant): The alpha-1 antitrypsin (AAT) deficiency is an autosomal recessive genetic disorder causing both liver and lung diseases, for which there is no effective treatment...
  11. Anti-inflammatory Serpin(AAT and Elafin) Gene Transfers*
    Sihong Song; Fiscal Year: 2003
    ..b>Alpha 1 antitrypsin (AAT) and elafin are serine proteinase inhibitors (serpin), and have anti-inflammatory properties...
  12. Irina Petrache; Fiscal Year: 2015
    ..b>Alpha 1 antitrypsin (A1AT) is an abundant protein released by the liver, with outreaching systemic actions...
  13. Andrew A Wilson; Fiscal Year: 2014
    ..Patients with alpha-1 antitrypsin (AAT) deficiency have decreases in circulating blood and lung epithelial lining fluid AAT that ultimately lead to ..
  14. Chengwen Li; Fiscal Year: 2016
    DESCRIPTION (provided by applicant): Alpha-1 antitrypsin (AAT) deficiency, due to the "piZZ" mutation, results in life-threatening lung and liver diseases in children and adults...
  15. Fine Mapping of COPD Susceptibility Genes
    Edwin K Silverman; Fiscal Year: 2012
    ..influenced by genetic factors, but the only proven genetic determinant of COPD is severe alpha 1-antitrypsin (AAT) deficiency...
  16. Wonder P Drake; Fiscal Year: 2014
    ..similar fashion, an association has been observed between disease severity among patients with Alpha-1-antitrypsin (AAT) deficiency and pathogenic bacteria...
  17. NGVL TOXICOLOGY LABORATORY
    Barry Byrne; Fiscal Year: 2006
    ..also performed a rodent toxicology study in support of a phase I trial of rAAV expressing the alpha 1-antitrypsin (AAT) gene vector, and a key study of the potential risk for carcinogenesis after IV injection in neonatal mice...
  18. Alpha-1 Antitrypsin Gene Therapy for Cystic Fibrosis
    Kenneth Brigham; Fiscal Year: 2001
    ..Abstract): The investigators have developed a plasmid vector that expresses the normal human alpha-1 antitrypsin (AAT) gene in human respiratory epithelium when delivered as a plasmid-cationic liposome complex...
  19. Treatment Decisions in Advanced Genetic Lung Disease
    SUSAN MCINNES; Fiscal Year: 2003
    DESCRIPTION: (Provided by the Applicant) Individuals with cystic fibrosis (CF) and alpha 1-antitrypsin (AAT) deficiency pulmonary disease face many difficult decisions throughout the course of their lives and illnesses...
  20. Development of Alpha-1 Antitrypsin Gene Therapeutic as Treatment for COPD
    Jonathan Sanders; Fiscal Year: 2005
    ..potency, anti-inflammatory effects, and efficacy in preventing or reversing emphysema by expression of the AAT gene in mice. Specific Aims: 1...
  21. GENETIC CONSTITUTIONS AND CANCER PREDISPOSITION
    HOPE PUNNETT; Fiscal Year: 1980
    The serum protease inhibitor alpha 1-antitrypsin (AAT) functions as a phase reactant neutralizer of proteolytic enzymes from tissues during inflammatory processes...
  22. Gene Therapy for Correction of PiZ Mutation
    Sihong Song; Fiscal Year: 2006
    Alpha 1-antitrypsin (AAT) is normally secreted from hepatocytes and circulates in the plasma, protecting lung elastin from degradation by neutrophil elastase. Deficiency of AAT can lead to emphysema...
  23. Alpha-1 Antitrypsin for Hereditary Deficiency
    Carol Ziomek; Fiscal Year: 2005
    ..production of rhAAT suitable for augmentation therapy of hereditary deficiency patients by: 1) characterizing the AAT transgene from transgenic founder goats that express rhAAT in their milk to select the best transgenic goat line ..
  24. A GENE BASED THERAPEUTIC FOR ACUTE LUNG INJURY
    Kenneth Brigham; Fiscal Year: 1999
    ..The AAT gene is delivered intravenously, using a specific plasmid-cationic liposome formulation that results in ..
  25. Function of a-1-Antitrypsin Receptor in Lung Disease
    William Balch; Fiscal Year: 2006
    ..from the failure of mutant soluble proteins to exit the endoplasmic reticulum (ER) including alpha-1-antitrypsin (a1AT) deficiency, a1AT, a serine proteinase inhibitor, functions to inhibit neutrophil elastase in the lung and prevent ..
  26. Genome-wide and Linkage Study of Quantitative Emphysema Phenotypes
    Stephen S Rich; Fiscal Year: 2010
    ..Mutations in the SERPINA1 gene cause panlobular emphysema but account for <1% of cases...
  27. Lisa A Maier; Fiscal Year: 2014
    ..by applicant): This proposal is in response to the request for application, RFA-12-013, "Genomic Research in AAT-Deficiency and Sarcoidosis study (GRADS)"...
  28. Laura L Koth; Fiscal Year: 2014
    DESCRIPTION (provided by applicant): Sarcoidosis and AAT are pulmonary diseases for which there is no cure and current medical therapies are not effective in many patients...
  29. Serap Aksoy; Fiscal Year: 2016
    ..In addition to HAT, wasting diseases in animals (known as animal African trypanosomiasis, AAT) are the primary reason for lack of agricultural development, adequate nutrition and economic prosperity in tsetse-..
  30. Influences of Parental Smoking on Pre-teen Reactivity to Smoking-Related Stimuli
    CATHERINE ANN FORESTELL; Fiscal Year: 2012
    ..children's tendency to approach and avoid smoking-related stimuli using a behavioral approach-avoidance task (AAT) designed for children...
  31. Inhibition of Autophagy Enhances Anti-Angiogenic Efficacy in Intracranial Glioma
    Martin M Pike; Fiscal Year: 2013
    ..Gliomas are highly vascular, but current anti-angiogenic therapy (AAT) induces only a transitory clinical benefit...
  32. Farrah Kheradmand; Fiscal Year: 2016
    ..specific T cells induce matrix metalloproteinase (MMP) 12 secretion in the lung that inhibits alpha 1 anti-trypsin (A1AT), thereby unleashing the activity of neutrophil elastase that cleaves elastin and weakens lung parenchyma...
  33. Recombinant alpha1-Antitrypsin Therapeutics
    XINLI HENRY LIN; Fiscal Year: 2010
    DESCRIPTION (provided by applicant): a1-antitrypsin (AAT;A1AT) deficiency is a common debilitating hereditary disorder...
  34. Preclinical &Phase I/II Trials of AAV-AAT Vectors
    Terence R Flotte; Fiscal Year: 2013
    ..An initial bridging clinical study of rAAV1-AAT via isolated limb perfusion (ILP) delivery is planned in the first year of the application...
  35. Susanta K Sarkar; Fiscal Year: 2015
    DESCRIPTION (provided by applicant): The early promise and hope for antiangiogenic therapy (AAT) in cancer has matured to a more realistic understanding that changes in the tumor microenvironment (TME) result in confounding effects that ..
  36. Kenneth D Tew; Fiscal Year: 2014
    ..In Aim 3 we will elaborate on preliminary observations that serpina1 and serpina3 are S- glutathionylated in the plasma of drug treated animals and may represent novel biomarkers for ..
  37. RGS Protein Regulation of G Protein Coupled Receptors
    John R Hepler; Fiscal Year: 2010
    ..indicate a prominent role for the functionally linked signaling proteins RGS2, Gq-alpha (Gqa), alpha-1A-adrenergic (a1A-AR) and m1 muscarininc cholinergic receptors (M1 AChR) in regulation of vascular hypertension, cardiac hypertrophy, ..
  38. ALAIN T LAEDERACH; Fiscal Year: 2016
    ..Mutations in specific genes including SERPINA1, which encodes [unreadable]- 1-antitrypsin, are associated with increased risk of developing COPD...
  39. Jann N Sarkaria; Fiscal Year: 2016
    DESCRIPTION (provided by applicant): Anti-angiogenic therapy (AAT) targeting the vascular endothelial growth factor (VEGF) axis is an important component of treatment for recurrent glioblastoma (GBM)...
  40. Protective signaling mechanisms of the alpha1A-adrenoceptor
    Dianne M Perez; Fiscal Year: 2013
    ..a1-AR subtypes (a1A, a1B and a1D) are G protein-coupled receptors that mediate the sympathetic nervous system by binding catecholamines...
  41. Paul A Johnston; Fiscal Year: 2014
    ..coactivator expression levels are associated with prostate cancer (CaP) recurrence after androgen ablation therapy (AAT)...
  42. KIMBERLY ANN FLEMING; Fiscal Year: 2014
    ..approach towards predictive cues will then be assessed in the laboratory using an Approach-Avoidance Task (AAT)...
  43. STUDIES OF NEURONAL AND GLIAL GLUTAMATE DECARBOXYLASES
    Jang Yen Wu; Fiscal Year: 1990
    ..serine-THM), cysteinesulfinic and cyteic acids decarboxylase (CSAD/CAD) and aspartate amino transferase (AAT) and glutaminase (GLNase), respectively...
  44. APPETITE FOCUSED CBWL FOR BINGE EATING DISORDERS
    Linda Craighead; Fiscal Year: 2001
    ..This intervention, Appetite Awareness Training (AAT), is designed to train clients to become more aware of moderate hunger and satiety cues and to teach them to shift ..
  45. ENGINEERING PRECURSOR SUPPLY FOR POLYKETIDE BIOSYNTHESIS
    Kevin Reynolds; Fiscal Year: 2003
    ..the role of propionyl CoA carboxylase, crotonyl CoA reductase, isobutyryl CoA mutase, and acetoacetyl CoA thiolase (AAT) in providing these precursors will be addressed...
  46. Murine Models of Presynaptic Neuromuscular Disease
    WILLIAM ATCHISON; Fiscal Year: 2009
    ..will be used to study neuromuscular transmission following passive transfer of LEMS to mice in which the a1A subunit of the P/Q-type of Ca channel is genetically-altered, either by deletion or point mutation, or in which the ..
  47. HEPATOCYTE GENE THERAPY FOR CITRULLINEMIA
    Brendan Lee; Fiscal Year: 2000
    ..At first, a recombinant adenovirus (Ad-AAT) expressing a serum reported gene product, alpha-antitrypsin (alpha1AT), will be delivered intravenously into normal neonatal calves...
  48. Quantitation Pulmonary Delivery of Therapeutic Protein
    Donna Palmer; Fiscal Year: 2005
    ..The initial target for our lead product (AZ-AAT) is hereditary emphysema...
  49. Hepatic engraftment of marrow cells in mice and humans
    Neil Theise; Fiscal Year: 2004
    ..defects will be tested by transplanting: female transgenic mice expressive of human abnormal (PiZ) a-1-antitrypsin (A1AT) with marrow from male mice expressive of human normal (PiM) A1AT (basolateral defect); female mdr2 knockout mice, ..
  50. METABOLIC AND HOMEOSTATIC MECHANISMS IN RETINA AND RPE
    Barry Winkler; Fiscal Year: 2003
    ..A third preferred substrate, glutamate, initially metabolized by the enzyme aspartate aminotransferase (AAT), has also been proposed...
  51. THOMAS VANVLEET; Fiscal Year: 2014
    ..project is to revise a prototype of a computerized attention training program (Amplified Attention Training, AAT) for hemispatial neglect completed in Phase I, and conduct a multi-site, randomized, controlled trial to establish ..
  52. NEUROSCIENCE OF NICOTINE DEPENDENCE AND COFACTORS
    Ovide Pomerleau; Fiscal Year: 2000
    ..progress in defining mechanisms for nicotine reinforcement at the molecular and animal level; understanding aat the human level, however, has lagged behind. The long-term objective is to help redress this deficiency...
  53. CARDIAC A1-ADENOSINE RECEPTOR RESERVE
    John Shryock; Fiscal Year: 2000
    ..adenosine to inhibit beta-ICa,L and to activate IKAdo in atrial myocytes: Aim #1 - distinct A1 receptor subtypes (A1a and A1b) subserve inhibition of beta-ICa,L and activation of IKAdo; Aim #2 - a single receptor is coupled to both ..
  54. INTERACTIONS OF CALCIUM CHANNELS WITH ADAPTOR PROTEINS
    Ilya Bezprozvanny; Fiscal Year: 2003
    ..The sites responsible for interaction of Q-type (a1A) Ca2+ channels with mint1 and CASK are localized in the immediate proximity to the position of polyglutamine repeat ..
  55. Oxidative Damage to DNA Repair Pathways
    Cameron Koch; Fiscal Year: 2006
    ..These effects are not seen in parental cells or A1A transfectants...
  56. Calcium Channels and Hereditary Ataxia
    Christopher Gomez; Fiscal Year: 2004
    ..The P/Q a subunit (a1A) encoded by the gene, CACNA1A, has been implicated in familial migraine, hereditary episodic ataxia and ..
  57. MECHANISM OF SELECTIVE EXPRESSION OF TRNA GENES
    KAREN SPRAGUE; Fiscal Year: 1999
    ..We will focus on two tRNA/A1a genes of silkworms, one of which (C) is transcribed constitutively, and the other (SG) only in silkglands...
  58. Information Retrieval for Large-scale Genomic Analysis
    Rimli Sengupta; Fiscal Year: 2001
    DESCRIPTION: (provided by applicant) This project supports the continuation of the PI1's interdisciplinary training started in September 1999 with a Sloan/DOE fellowship in Computational Molecular Biology...
  59. AUTOMATED ANNOTATION OF GENOMIC DNA SEQUENCES
    Xiaoqiu Huang; Fiscal Year: 2000
    ..The investigators will improve an analysis and annotation tool (AAT) that uses fast database searching and rigorous alignment to locate exons of the genomic sequence and to define ..
  60. INTENSITY OF SLEEP OVER THE HUMAN LIFE SPAN
    HAROLD ZEPELIN; Fiscal Year: 1992
    ..about age-related reduction of sleep's intensity that is indicated by lowering of the auditor awakening threshold (AAT) and deterioration of delta (slow wave) activity in the EEG...
  61. GENES WHICH POSITIVELY REGULATE TUMOR CELL METASTASIS
    JACQUELINE TESTA; Fiscal Year: 1992
    ..To recover the cDNA, total DNA isolated from the recovered metastatic transfectants will be cut with Aat II, an enzyme which recognizes a unique restriction site in the pRc/RSV vector...
  62. PROTEASE INHIBITORS AND LPS INDUCED FEVER
    CAROLE CONN; Fiscal Year: 1999
    Studies in this proposal focus on the mechanism by which the acute-phase proteins a1-antitrypsin (AAT) and a2-macroglobulin (AMG) act as positive modulators of fever...