Faculty Collaboration Database

The peroxynitrite generator, SIN-1, becomes a nitric oxide donor in the presence of electron acceptors. Arch Biochem Biophys 1999 Jan 15;361(2):331-9

Date

01/12/1999

Pubmed ID

9882464

DOI

10.1006/abbi.1998.1007

Scopus ID

2-s2.0-0033555139 (requires institutional sign-in at Scopus site)   131 Citations

Abstract

SIN-1 has been used, in vitro, to simultaneously generate nitric oxide (*NO) and superoxide (O*-2). However, the pharmacological activity of SIN-1 resembles that of a *NO donor. SIN-1 decays by a three-step mechanism. After initial isomerization to an open ring form, SIN-1A reduces oxygen by a one-electron transfer reaction to give O*-2 and the SIN-1 cation radical, which decomposes to form SIN-1C and *NO. Here we report that one-electron oxidizing agents, in addition to oxygen, can oxidize SIN-1A, resulting in the release of *NO without the concomitant formation of O*-2. We demonstrate that easily reducible nitroxides, such as the nitronyl and imino nitroxides, are able to oxidize SIN-1. Biological oxidizing agents such as ferricytochrome c also stimulate *NO production from SIN-1. In addition, decomposition of SIN-1 by human plasma or by the homogenate of rat liver, kidney, and heart tissues results in the formation of *NO. Our findings suggest that SIN-1 may react with heme proteins and other electron acceptors in biological systems to produce *NO. Thus, at the relatively low in vivo oxygen concentrations, SIN-1 is likely to behave more like an *NO donor than a peroxynitrite donor. The relevance of this reaction to myocardial protection afforded by SIN-1 in ischemia/reperfusion-induced injury is discussed.

Author List

Singh RJ, Hogg N, Joseph J, Konorev E, Kalyanaraman B

Authors

Neil Hogg PhD Associate Dean, Professor in the Biophysics department at Medical College of Wisconsin
Balaraman Kalyanaraman PhD Professor in the Biophysics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Cyclic N-Oxides
Free Radical Scavengers
Hemeproteins
Humans
Imidazoles
Kidney
Liver
Molsidomine
Myocardium
Nitrates
Nitric Oxide Donors
Oxidants
Rats