Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.37 (neutrophil elastase)
 4,078 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Emphysema is a chronic pulmonary disorder characterized by a permanent enlargement of the air spaces distal to the terminal bronchioles consequent to destruction of the alveolar walls, including the epithelial and endothelial cells and the connective tissue matrix. There is increasing evidence that an imbalance of oxidants and antioxidants in the lower respiratory tract contributes to this process. Oxidants such as O2-., H2O2, OH, OCl- are generated in the lower respiratory tract as a result of normal biochemical processes, activation of inflammatory cells and inhaled toxic gases. Under normal circumstances, the parenchymal cells are protected by intracellular antioxidants and membrane radical scavengers. In addition, the fluid lining the epithelial surface contains a catalase-like antioxidant that protects the epithelial cells from oxidants. If the oxidant burden overcomes these defenses, the parenchymal cells may be injured, the connective tissue matrix may be partially degraded, the antiprotease screen that protects the lower respiratory tract from attack by neutrophil elastase may be rendered impotent. The alveolar wall then becomes highly vulnerable to elastolytic attack, with a complete destruction of the interstitial connective tissue matrix. In this regard, it is reasonable to hypothesize that reestablishment of the oxidant-antioxidant balance in favor of the antioxidants would be useful as a therapeutic strategy to suppress the emphysematous process.
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PMID:Oxidants, antioxidants and the pathogenesis of emphysema. 299 6

Alpha-1-protease inhibitor (alpha-1-PI) is the major regulator of extracellular leukocyte elastase activity and can be rendered impotent against elastase by oxidation of a critical methionine, residue 358. Alpha-1-PI was isolated from rat plasma by affinity chromatography on Sepharose-bound anhydrochymotrypsin, DEAE-cellulose anion-exchange, and Sephadex G-150 gel filtration. The product was radiolabeled using non-oxidative conditions with Bolton-Hunter reagent, and an aliquot subsequently oxidized with N-chlorosuccinimide. Turnover studies in rats indicated that both native and oxidized alpha-1-PI had half-lives of 170 min. Using partially purified human neutrophil methionine sulfoxide-peptide reductase (Met(O)PR), it was demonstrated that oxidized product could be converted back "in vitro" to an active inhibitor of elastase. To assess whether oxidized alpha-1-PI underwent reduction "in vivo," methionine-oxidized rat inhibitor was injected into the rats, aliquots of plasma samples were withdrawan and passed through a Sepharose-bound anhydrochymotrypsin affinity resin, and bound functional alpha-1-PI was eluted with 0.1 M chymostatin. Radioactive counting of bound and unbound fractions indicated that reduction does not occur in vivo and suggested that, at least under homeostatic conditions, the Met(O)PR is confined to intracellular sites where it does not have access to the circulating protein.
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PMID:Studies on the turnover of methionine oxidized alpha-1-protease inhibitor in rats. 349 3