Different effects of SNP and GSNO on mitochondrial O2 .- /H 2O2 production.

Sodium Nitroprusside (SNP) and S-Nitrosoglutathione (GSNO) differently affect mitochondrial H(2)O(2) 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 ((.)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 (.)NO release) induces an inhibition of the succinate dependent H(2)O(2) production consistent with a (.)NO dependent covalent modification. However maximal inhibition of the succinate dependent H(2)O(2) release is obtained in the presence of low GSNO (20-100 μM), but not with SNP. This inhibition appears independent of (.)NO release since μM GSNO does not affect mitochondrial respiration, or the H(2)O(2) detection systems and its effect is very rapid. Inhibition may be partly due to an increased removal of O (2) (.-) since GSNO chemically competes with NBT and cytochrome C in O (2) (.-) detection.