Nitric oxide promotes oxygen free radicals release in heart mitochondria and submitochondrial particles

PODEROSO, JJ, CARRERAS, MC, LISDERO, C, SCHÖPFER, F, RIOBÓ, N, BOVERIS, A.

The Biology of Nitric Oxide, Part. 5

Año: 1996; p. 121 - 121

Exogenous nitric oxide (NO) and peroxynitrite can depress enzymes like aconitase and cytochrome c oxidase. Since effects of NO could alter O2 radicals production by mitochondria, the main purpose of this study was to measure these compounds in rat and beef heart organelles and submitochondrial particles exposed to the NO donor S-nitrosogluthatione (GSNO). Incubation of mitochondria with 25-150 µM GSNO and 50 µM dithiothreitol increased release of hydrogen peroxide (H2O2) in a dose-dependent manner with succinate alone as substrate and even more after addition of 2 µM antimycin A (AA). The same effect was observed respect to both superoxide anion (O2-) and H2O2 in the isolated rat and beef heart submitochondrial membranes. In absence of GSNO, the control mitochondria and particles showed no detectable H2O2 or O2- release with succinate alone but a similar response to AA. Activation of the rat heart particles with succinate alone or plus AA abolished, but superoxide dismutase restores, the electrochemical detection of NO released by GSNO/DTT, confirming the formation of ONOO-. Simultaneously, GSNO inhibited cytochrome c oxidase activity in submitochondrial particles with a half-inhibitory concentration of about 10 µM GSNO; the effect was reversed by adding 6 mM succinate. The results suggest that NO exerts an antimycin-like effect and increases O2 free radicals release by mitochondrial membranes and that, in that condition, an excess of O2 free radicals lead to formation of ONOO- and removal of NO as a self-regulatory process.