Nitric oxide inhibits H 2 O 2 -induced transferrin receptor-dependent apoptosis in endothelial cells: Role of ubiquitin-proteasome pathway
- 4 September 2003
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 100 (19), 10653-10658
- https://doi.org/10.1073/pnas.1933581100
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. Nomega-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.Keywords
This publication has 46 references indexed in Scilit:
- NCX‐4016, a nitric oxide‐releasing aspirin, protects endothelial cells against apoptosis by modulating mitochondrial functionThe FASEB Journal, 2002
- Transferrin Receptor-dependent Iron Uptake Is Responsible for Doxorubicin-mediated Apoptosis in Endothelial CellsPublished by Elsevier BV ,2002
- Hydrogen Peroxide Activates Endothelial Nitric-oxide Synthase through Coordinated Phosphorylation and Dephosphorylation via a Phosphoinositide 3-Kinase-dependent Signaling PathwayPublished by Elsevier BV ,2002
- IRP1 Activation by Extracellular Oxidative Stress in the Perfused Rat LiverPublished by Elsevier BV ,2001
- Inhibition of Oxidized Low-density Lipoprotein-induced Apoptosis in Endothelial Cells by Nitric OxidePublished by Elsevier BV ,2001
- Inactivation of Both RNA Binding and Aconitase Activities of Iron Regulatory Protein-1 by Quinone-induced Oxidative StressPublished by Elsevier BV ,1999
- THE UBIQUITIN SYSTEMAnnual Review of Biochemistry, 1998
- Mechanistic Studies on the Inactivation of the Proteasome by Lactacystin in Cultured CellsPublished by Elsevier BV ,1997
- Iron-sulfur clusters as biosensors of oxidants and ironTrends in Biochemical Sciences, 1996
- Effects of peroxynitrite‐induced protein modifications on tyrosine phosphorylation and degradationFEBS Letters, 1996