Medical College of Wisconsin
CTSICores SearchResearch InformaticsREDCap

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

09/06/2003

Pubmed ID

12958216

Pubmed Central ID

PMC196859

DOI

10.1073/pnas.1933581100

Scopus ID

2-s2.0-0141703321 (requires institutional sign-in at Scopus site)   95 Citations

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.

Author List

Kotamraju S, Tampo Y, Keszler A, Chitambar CR, Joseph J, Haas AL, Kalyanaraman B

Authors

Balaraman Kalyanaraman PhD Professor in the Biophysics department at Medical College of Wisconsin
Agnes 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 Hydratase
Animals
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