Faculty Collaboration Database

Production of hydroxyl radicals from the simultaneous generation of superoxide and nitric oxide. Biochem J 1992 Jan 15;281 ( Pt 2)(Pt 2):419-24

Date

01/15/1992

Pubmed ID

1310595

Pubmed Central ID

PMC1130701

DOI

10.1042/bj2810419

Scopus ID

2-s2.0-0026500329 (requires institutional sign-in at Scopus site)   647 Citations

Abstract

Both nitric oxide (NO) and superoxide are generated by macrophages, neutrophils and endothelial cells. It has been postulated that the generation of these two radicals under physiological conditions can lead to the formation of peroxynitrite and (as a result of the homolytic lysis of this molecule) the production of hydroxyl radicals. We have used 3-morpholinosydnonimine N-ethylcarbamide (SIN-1), a sydnonimine capable of generating both NO and superoxide simultaneously, to test this hypothesis. SIN-1 (1 mM) generated superoxide and NO at rates of 7.02 microM/min and 3.68 microM/min respectively in phosphate-buffered saline, pH 7.2, at 37 degrees C. Incubation of SIN-1 with both deoxyribose and sodium benzoate resulted in the formation of malondialdehyde (MDA). In addition, the incubation of SIN-1 with sodium benzoate resulted in the production of compounds with fluorescence emission spectra characteristic of hydroxylated products. Both the production of MDA and the generation of fluorescent compounds were inhibited by the hydroxyl radical scavenger mannitol. In all the above respects, SIN-1 mimicked the production of hydroxyl radicals from the ascorbate-driven Fenton reaction. Catalase had no effect on the SIN-1-dependent generation of MDA, and superoxide dismutase was partially inhibitory. SIN-1 produces an oxidant with the properties of the hydroxyl radical by a mechanism clearly different to that of the Fenton reaction. We conclude that the simultaneous production of NO and superoxide from SIN-1 results in the formation of hydroxyl radicals.

Author List

Hogg N, Darley-Usmar VM, Wilson MT, Moncada S

Author

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

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

Benzoates
Benzoic Acid
Deoxyribose
Ethanol
Free Radical Scavengers
Free Radicals
Hydroxides
Hydroxyl Radical
Kinetics
Malondialdehyde
Molsidomine
Nitric Oxide
Oxidation-Reduction
Superoxides