Nitric oxide inhibits H2O2-induced transferrin receptor-dependent apoptosis in endothelial cells: Role of ubiquitin-proteasome pathway. Proc Natl Acad Sci U S A 2003 Sep 16;100(19):10653-8
Date
09/06/2003Pubmed ID
12958216Pubmed Central ID
PMC196859DOI
10.1073/pnas.1933581100Scopus ID
2-s2.0-0141703321 (requires institutional sign-in at Scopus site) 95 CitationsAbstract
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.
Author List
Kotamraju S, Tampo Y, Keszler A, Chitambar CR, Joseph J, Haas AL, Kalyanaraman BAuthors
Balaraman Kalyanaraman PhD Professor in the Biophysics department at Medical College of WisconsinAgnes Keszler PhD Research Scientist I in the Biophysics department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
Aconitate HydrataseAnimals
Apoptosis
Cattle
Cysteine Endopeptidases
Endothelium, Vascular
Glutathione
Hydrogen Peroxide
Iron Regulatory Protein 1
Multienzyme Complexes
Nitric Oxide
Oxidative Stress
Proteasome Endopeptidase Complex
Receptors, Transferrin
Ubiquitin