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| PRODUCTION OF HYDROXYL RADICALS FROM THE SIMULTANEOUS GENERATION OF SUPEROXIDE AND NITRIC-OXIDE |
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| Author(s): HOGG N, DARLEYUSMAR VM, WILSON MT, MONCADA S |
| Source: BIOCHEMICAL JOURNAL Volume: 281 Pages: 419-424 Part: Part 2 Published: JAN 15 1992 |
| Times Cited: 544 References: 23 |
| 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-I (1 mM) generated superoxide and NO at rates of 7.02-mu-M/min and 3.68-mu-M/min respectively in phosphate-buffered saline, pH 7.2, at 37-degrees-C. Incubation of SIN-I with both deoxyribose and sodium benzoate resulted in the formation of malondialdehyde (MDA). In addition, the incubation of SIN-I 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. |
| Document Type: Article |
| Language: English |
Addresses:
1. WELLCOME RES LABS, LANGLEY COURT, BECKENHAM BR3 3BS, KENT ENGLAND
2. UNIV ESSEX, DEPT CHEM & BIOL CHEM, COLCHESTER CO4 3SQ, ESSEX ENGLAND |
| Publisher: PORTLAND PRESS, 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ |
| Subject Category: Biochemistry & Molecular Biology |
| IDS Number: HB615 |
| ISSN: 0264-6021 |
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