Alpha-1 antitrypsin and lung cell apoptosis

Karina A. Serban, Irina Petrache

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Discovery of alpha-1 antitrypsin (A1AT) as the principal circulating inhibitor of neutrophil elastase was critical to the appreciation of protease/antiprotease imbalance involvement in the pathogenesis of emphysema. Additional targets of A1AT have been uncovered, along with their contribution to alveolar wall destruction induced by cigarette smoke exposure. We highlight in this report mechanisms of A1AT antiapoptotic effects on structural lung endothelial cells. This function was largely dependent on uptake of the protein from the circulation via clathrin-and, in part, caveolae-mediated endocytosis and on specific interactions with cysteine proteases such as capsase-3, -6, and -7. Exposures to cigarette smoke diminished A1AT intracellular uptake and its anticaspase action, suggesting that even in A1AT-suficient individuals, cigarette smoke may weaken the serpin's endothelial prosurvival effect. In addition, cigarette smoke exposure or genetic mutations known to induce posttranslational modifications such as oxidation or polymerization may alter A1AT bidirectional intracellular traffic in endothelial cells and thus determine its functional bioavailability in certain lung compartments. Uncovering and harnessing the A1AT canonical and noncanonical mechanisms will advance our understanding of the pathogenesis of emphysema and may provide means to improve the effectiveness of therapies in both A1AT-sufficient and A1AT-deficient individuals.

Original languageEnglish (US)
Pages (from-to)S146-S149
JournalAnnals of the American Thoracic Society
Volume13
DOIs
StatePublished - Apr 1 2016
Externally publishedYes

Fingerprint

alpha 1-Antitrypsin
Apoptosis
Lung
Smoke
Tobacco Products
Emphysema
Endothelial Cells
Secretory Proteinase Inhibitory Proteins
Serpins
Caveolae
Clathrin
Cysteine Proteases
Post Translational Protein Processing
Endocytosis
Protease Inhibitors
Polymerization
Biological Availability
Peptide Hydrolases
Mutation

Keywords

  • Alpha-1 antitrypsin
  • Apoptosis
  • Caspase
  • Cigarette smoke
  • Emphysema

ASJC Scopus subject areas

  • Medicine(all)
  • Pulmonary and Respiratory Medicine

Cite this

Alpha-1 antitrypsin and lung cell apoptosis. / Serban, Karina A.; Petrache, Irina.

In: Annals of the American Thoracic Society, Vol. 13, 01.04.2016, p. S146-S149.

Research output: Contribution to journalArticle

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