Nitric oxide inhibits H2O2-induced transferrin receptor-dependent apoptosis in endothelial cells: Role of ubiquitin-proteasome pathway
Abstract
We investigated here the mechanism of cytoprotection of nitric oxide (•NO) in bovine aortic endothelial cells treated with H2O2. NONOates were used as •NO donors that released •NO 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 inhibited the TfR-mediated iron uptake, dichlorofluorescein fluorescence, and apoptosis in H2O2-treated cells. •NO increased the proteasomal activity and degradation of nitrated TfR via ubiquitination. Nω-nitro-L-arginine methyl ester, a nonspecific inhibitor of endogenous •NO biosynthesis, decreased the trypsin-like activity of 26S proteasome. •NO, 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.
- Publication:
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Proceedings of the National Academy of Science
- Pub Date:
- September 2003
- DOI:
- 10.1073/pnas.1933581100
- Bibcode:
- 2003PNAS..10010653K
- Keywords:
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- BIOCHEMISTRY