[Possible role of glutathione peroxidase in the regulation of collagenase activity].
Glutathione peroxidase (Se-GPx) is a selenoenzyme which catalyzes the reduction of hydroperoxides by glutathione (GSH), in most mammalian cells. Several Slow-acting drugs that are used in the treatment of rheumatoid arthritis, including D-Penicillamine, alpha-mercaptopropionylglycine and gold salts, are specific inhibitors of Se-GPx. In situation of oxidant stress, Se-GPx activity is a major source of glutathione disulfide (GSSG), an essential activator of leucocyte collagenase. Hence the possibility that the enzymatic reduction of hydroperoxides produced during chronic inflammation would play an important role in the destruction of joint tissue of arthritic patients. Inhibition of a protective system such as Se-GPx may therefore be involved in the mechanism of action of D-Penicillamine and gold salts, but it could also explain some of their undesirable or toxic effects. Confirmation of this hypothesis would open the way to new pharmacological strategies.
D001172:Arthritis, Rheumatoid / Q000209:etiology; D004790:Enzyme Induction / Q000187:drug effects; D005609:Free Radicals; D005978:Glutathione / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D019803:Glutathione Disulfide; D005979:Glutathione Peroxidase / Q000037:antagonists & inhibitors / Q000502:physiology*; D006801:Humans; D003012:Microbial Collagenase / Q000096:biosynthesis / Q000378:metabolism*; D009504:Neutrophils / Q000201:enzymology
D005609:Free Radicals; D005979:Glutathione Peroxidase; D003012:Microbial Collagenase; D005978:Glutathione; D019803:Glutathione Disulfide
Rôle possible de la glutathion peroxydase dans la régulation de l'activité collagénase.