Superoxide activates constitutive nitric oxide synthase in a brain particulate fraction.
Nitric oxide (*NO) can act as an antioxidant by directly scavenging reactive free radicals, inhibiting the oxidative chemistry of iron, and signaling the up-regulation of antioxidant enzymes. However, the cellular utility of *NO as an antioxidant requires that constitutive nitric oxide synthase (NOS) be activated rapidly by a signal(s) for oxidant formation. We report here that superoxide (O2*-), added directly as potassium superoxide (KO2), produced a superoxide dismutase-sensitive and hydrogen peroxide-independent stimulation of NOS activity, measured by the conversion of [3H]arginine to [3H]citrulline and nitrite formation, in a synaptic particulate fraction from rat brain cerebral cortex. O2*- produced maximal activation of NOS in the presence of the antioxidant urate and ATP. Stimulation of NOS activity by O2*- was abolished by N-monomethyl-L-arginine and by the Ca2+ chelator EGTA but not by 7-nitroindazole, which would be expected to inhibit neuronal NOS. We propose that limited activation of NOS by O2*- may be an important contributor to brain oxidant defenses and, more generally, a signal for cellular adaptation and survival, although excessive generation of nitrogen oxides would be expected to produce neurotoxicity.
McPherson
Deanne B
DB
Department of Chemistry, 800 Linden Street, University of Scranton, Scranton, PA 18510, USA.
Kilker
Ryan P
RP
Foley
Timothy D
TD
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000201:enzymology*; D002458:Cell Fractionation; D002956:Citrulline / Q000378:metabolism; D015224:Dideoxynucleosides; D004789:Enzyme Activation; D007527:Isoenzymes / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D009607:Nitrosourea Compounds; D011489:Protein Denaturation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013451:Sulfonic Acids / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*
D015224:Dideoxynucleosides; D007527:Isoenzymes; D009607:Nitrosourea Compounds; D013451:Sulfonic Acids; D013481:Superoxides; D002956:Citrulline; D000255:Adenosine Triphosphate; C048808:3' (3-(2-chloroethyl)-3-nitrosoureido)-2',3'-dideoxyuridine; D019001:Nitric Oxide Synthase; D013482:Superoxide Dismutase