Exp Mol Med.  1998 Dec;30(4):221-226.

The effects of oxygen radicals on the activity of nitric oxide synthase and guanylate cyclase

• Kim SM
• Byun JS
• Jung YD
• Kang IC
• Choi SY
• Lee KY

Abstract

Reactive oxygen species such as superoxides, hydrogen peroxide (H2O2) and hydroxyl radicals have been suggested to be involved in the catalytic action of nitric oxide synthase (NOS) to produce NO from L-arginine. An examination was conducted on the effects of oxygen radical scavengers and oxygen radical-generating systems on the activity of neuronal NOS and guanylate cyclase (GC) in rat brains and NOS from the activated murine macrophage cell line J774. Catalase and superoxide dismutase (SOD) showed no significant effects on NOS or GC activity. Nitroblue tetrazolium (NBT, known as a superoxide radical scavenger) and peroxidase (POD) inhibited NOS, but their inhibitory actions were removed by increasing the concentration of arginine or NADPH respectively, in the reaction mixture. NOS and NO-dependent GC were inactivated by ascorbate/FeSO4 (a metal-catalyzed oxidation system), 2'2'-azobis-amidinopropane (a peroxy radical producer), and xanthine/xanthine oxidase (a superoxide generating system). The effects of oxygen radicals or antioxidants on the two isoforms of NOS were almost similar. However, H2O2 activated GC in a dose-dependent manner from 100 microM to 1 mM without significant effects on NOS. H2O2-induced GC activation was blocked by catalase. These results suggested that oxygen radicals inhibited NOS and GC, but H2O2 could activate GC directly.

Keyword

Oxygen radicals; hydrogen peroxide; NO synthase; guanylate cyclase

MeSH Terms

Animal
Antioxidants/pharmacology
Brain/enzymology
Catalase/pharmacology
Cell Line
Guanylate Cyclase/metabolism*
Hydrogen Peroxide/pharmacology
Macrophages/enzymology
NADP/pharmacology
Nitric-Oxide Synthase/metabolism*
Nitroblue Tetrazolium/pharmacology
Rats
Rats, Sprague-Dawley
Reactive Oxygen Species/metabolism*
Signal Transduction
Superoxide Dismutase/pharmacology