Peroxynitrite-induced protein nitration is responsible for renal mitochondrial damage in diabetic rat

Oxidative stress, especially mediated by peroxynitrite (ONOO-), plays a key role in diabetes. Mitochondria, as the generating source of ONOO-, may also be the major damaging target of ONOO-. Whether ONOO--induced protein nitration is responsible for renal mitochondrial damage in diabetes is not fully known. This study was aimed to clarify the relationship between nitration of entire mitochondrial proteins induced by ONOO- and the renal mitochondrial damage in diabetes. Sprague-Dawley male rats were injected ip with streptozotocin to induce diabetes. After 10 weeks, inducible nitric oxide synthase (iNOS) mRNA expression and protein content in renal cortex were detected. Distribution of nitrotyrosine (NT), a specific marker of ONOO-, in renal cortex and NT content in mitochondrial proteins were detected. The ultrastructure of glomerulus was observed. Aminoguanidine was used as a selective inhibitor of iNOS to reduce the derivation of ONOO-. In diabetic rat, increasing levels of iNOS mRNA and protein content, and NT content were observed, in accord with the pathological alterations of glomerulus. In aminoguanidine group, these alterations were attenuated significantly. In conclusion, ONOO- could induce entire mitochondrial proteins nitration, responsible for the damage of renal mitochondria in diabetes. (J. Endocrinol. Invest. 33: 140-146, 2010) (C) 2010, Editrice Kurtis