Nitric oxide inhibits H2O2-induced transferrin receptor-dependent apoptosis in endothelial cells:: Role of ubiquitin-proteasome pathway

We investigated here the mechanism of cytoprotection of nitric oxide ((NO)-N-.) in bovine aortic endothelial cells treated with H2O2.NONOates were used as (NO)-N-. donors that released (NO)-N-. slowly at a well defined rate in the extracellular and intracellular milieus. H2O2-mediated intracellular dichlorofluorescein fluorescence and apoptosis were enhanced by the transferrin receptor (TfR)-mediated iron uptake. (NO)-N-. inhibited the TfR-mediated iron uptake, dichlorofluorescein fluorescence, and apoptosis in H2O2-treated cells. (NO)-N-. increased the proteasomal activity and degradation of nitrated TfR via ubiquitination. N-omega-nitro-L-arginine methyl ester, a nonspecific inhibitor of endogenous (NO)-N-. biosynthesis, decreased the trypsin-like activity of 26S proteasome. (NO)-N-., by activating proteolysis, mitigates TfR-dependent iron uptake, dichlorodihydrofluorescein oxidation, and apoptosis in H2O2-treated bovine aortic endothelial cells. The relevance of biological nitration on redox signaling is discussed.