Different effects of SNP and GSNO on mitochondrial O^sub 2^^sup .-^/H2O2 production

Sodium Nitroprusside (SNP) and S-Nitrosoglutathione (GSNO) differently affect mitochondrial H2O2 release at Complex-I. mM SNP increases while GSNO decreases the release induced by succinate alone or added on top of NAD-linked substrates. Stimulation likely depends on Nitric Oxide (^sup .^NO) (released by SNP but not by GSNO) inhibiting cytochrome oxidase and mitochondrial respiration. Preincubations with SNP or high GSNO (10 mM plus DTE to increases its ^sup .^NO release) induces an inhibition of the succinate dependent H2O2 production consistent with a ^sup .^NO dependent covalent modification. However maximal inhibition of the succinate dependent H2O2 release is obtained in the presence of low GSNO (20-100 μM), but not with SNP. This inhibition appears independent of ^sup .^NO release since μM GSNO does not affect mitochondrial respiration, or the H2O2 detection systems and its effect is very rapid. Inhibition may be partly due to an increased removal of O^sub 2^^sup .-^ since GSNO chemically competes with NBT and cytochrome C in O^sub 2^^sup .-^ detection.[PUBLICATION ABSTRACT]