Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Peroxynitrite (ONOO-) is a potent inhibitor of myocardial aconitase. Because ONOO- reacts with sulfhydryl moieties, we investigated whether thiols protect against ONOO(-)-mediated inhibition of aconitase. Aconitase activity was examined in ventricular homogenates prepared from freshly isolated rat hearts. Peroxynitrite, but not the nitric oxide donor S-nitroso-N-acetyl-d,l-penicillamine (0.03-300 microM), inhibited aconitase activity (IC50 = 47 +/- 6 microM). L-Cysteine (0.03-3 mM), glutathione (0.03-3 mM), and N-(2-mercaptoproprionyl)-glycine (MPG, 0.1-3 mM) protected against the inhibitory effect of ONOO- (100 microM) with the rank order of potency of MPG > glutathione > L-cysteine. D-Cysteine (3 mM) had a protective effect similar to L-cysteine, but L-cystine, the oxidized form of L-cysteine, offered no protection. Ferrous ammonium sulfate (1 mM) markedly enhanced the protection provided by L-cysteine, but not by glutathione or MPG. Thiols protect myocardial aconitase against inhibition by ONOO- in a manner which is sulfhydryl group dependent and not stereospecific. The protection is related to the maintenance of the redox state of the iron-sulfur cubane cluster and cysteine residues at the active site of the enzyme. Both naturally occurring thiols and thiol-based drugs may be useful to protect the heart during ischemia-reperfusion injury where there is an excessive production of ONOO-.
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PMID:Thiols protect the inhibition of myocardial aconitase by peroxynitrite. 946 26