The effect of catalase and methionine-S-oxide reductase on oxidised alpha 1-proteinase inhibitor.
Oxidative damage to alpha 1-proteinase inhibitor (alpha 1-PI) may be important in the pathogenesis of emphysema. We have studied the ability of 2 enzymes (catalase and methionine-S-oxide reductase) to prevent and reverse oxidation of alpha 1-PI by hydrogen peroxide. Pre-incubation of catalase with H2O2 protected alpha 1-PI from oxidation, but the enzyme could not reverse prior oxidation of alpha 1-PI. In contrast, methionine-S-oxide reductase fully restored activity to H2O2-oxidised alpha 1-PI. Sputum sol-phase from smokers and non-smokers contained alpha 1-PI that was only about 30% active. Functional activity increased in both smokers (p less than 0.025) and non-smokers (p less than 0.05) approximately 2-fold following incubation with the reductase. Western blotting of the samples showed that about 20% of the alpha 1-PI was present as an enzyme-inhibitor complex and 20% was proteolytically cleaved. These observations suggest proteolysis, complexing with enzyme and oxidation are mechanisms of inactivation of alpha 1-PI in lung secretions.
D001798:Blood Proteins / Q000378:metabolism*; D002374:Catalase / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide; D007163:Immunosorbent Techniques; D066298:In Vitro Techniques; D051150:Methionine Sulfoxide Reductases; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000378:metabolism*; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors; D011480:Protease Inhibitors / Q000378:metabolism*; D012907:Smoking; D000515:alpha 1-Antitrypsin
D001798:Blood Proteins; D011480:Protease Inhibitors; D000515:alpha 1-Antitrypsin; D006861:Hydrogen Peroxide; D010088:Oxidoreductases; D002374:Catalase; D051150:Methionine Sulfoxide Reductases; C027219:methionine sulfoxide reductase; D010196:Pancreatic Elastase