| Lung disease associated with alpha1-antitrypsin deficiency. | |
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MedLine Citation:
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PMID: 21030517 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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α(1)-Antitrypsin (A1AT) is a polyvalent, acute-phase reactant with an extensive range of biological functions that go beyond those usually linked to its antiprotease (serpin) activities. Genetic mutations cause a systemic deficiency of A1AT, leading to liver and pulmonary diseases, including emphysema and chronic bronchitis. The pathogenesis of emphysema, which involves the destruction of small airway structures and alveolar units, is triggered by cigarette smoke and pollutants. The tissue damage caused by these agents is further potentiated by the mutual interactions between apoptosis, oxidative stress, and protease/antiprotease imbalance. These processes lead to the activation of endogenous mediators of tissue destruction, including the lipid ceramide, extracellular matrix proteins, and abnormal inflammatory cell signaling. In this review, we propose that A1AT has a range of actions that are not restricted to protease inhibition but rather extend to mitigate a range of these pathological processes involved in the development of emphysema. We discuss the evidence indicating that A1AT blocks apoptosis by binding and inhibiting active caspase-3 and modulates a broad range of inflammatory responses induced by neutrophils and by lipopolysaccharide and tumor necrosis factor-α signaling. |
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Authors:
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Rubin M Tuder; Sabina M Janciauskiene; Irina Petrache |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Review |
Journal Detail:
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Title: Proceedings of the American Thoracic Society Volume: 7 ISSN: 1943-5665 ISO Abbreviation: Proc Am Thorac Soc Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-10-29 Completed Date: 2011-03-17 Revised Date: 2011-11-01 |
Medline Journal Info:
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Nlm Unique ID: 101203596 Medline TA: Proc Am Thorac Soc Country: United States |
Other Details:
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Languages: eng Pagination: 381-6 Citation Subset: IM |
Affiliation:
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Program in Translational Lung Research, Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado at Denver, Aurora, Colorado, USA. Rubin.Tuder@UCDenver.Edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Apoptosis Caspase 3 / metabolism Emphysema / physiopathology* Humans Pulmonary Disease, Chronic Obstructive / physiopathology* alpha 1-Antitrypsin Deficiency / metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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HL66554/HL/NHLBI NIH HHS; P01 1P50 HL084945/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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EC 3.4.22.-/Caspase 3 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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