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Thiols protect the inhibition of myocardial aconitase by peroxynitrite.
Arch Biochem Biophys. 1998 Feb 01; 350(1):104-8.AB

Abstract

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-.

Authors+Show Affiliations

Department of Pediatrics, University of Alberta, Edmonton, Canada.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

9466826

Citation

Cheung, P Y., et al. "Thiols Protect the Inhibition of Myocardial Aconitase By Peroxynitrite." Archives of Biochemistry and Biophysics, vol. 350, no. 1, 1998, pp. 104-8.
Cheung PY, Danial H, Jong J, et al. Thiols protect the inhibition of myocardial aconitase by peroxynitrite. Arch Biochem Biophys. 1998;350(1):104-8.
Cheung, P. Y., Danial, H., Jong, J., & Schulz, R. (1998). Thiols protect the inhibition of myocardial aconitase by peroxynitrite. Archives of Biochemistry and Biophysics, 350(1), 104-8.
Cheung PY, et al. Thiols Protect the Inhibition of Myocardial Aconitase By Peroxynitrite. Arch Biochem Biophys. 1998 Feb 1;350(1):104-8. PubMed PMID: 9466826.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Thiols protect the inhibition of myocardial aconitase by peroxynitrite. AU - Cheung,P Y, AU - Danial,H, AU - Jong,J, AU - Schulz,R, PY - 1998/2/19/pubmed PY - 1998/2/19/medline PY - 1998/2/19/entrez SP - 104 EP - 8 JF - Archives of biochemistry and biophysics JO - Arch Biochem Biophys VL - 350 IS - 1 N2 - 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-. SN - 0003-9861 UR - https://www.unboundmedicine.com/medline/citation/9466826/Thiols_protect_the_inhibition_of_myocardial_aconitase_by_peroxynitrite_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0003-9861(97)90496-3 DB - PRIME DP - Unbound Medicine ER -