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) 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.
Kotamraju
Srigiridhar
S
Biophysics Research Institute and Free Radical Research Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Tampo
Yoshiko
Y
Keszler
Agnes
A
Chitambar
Christopher R
CR
Joseph
Joy
J
Haas
Arthur L
AL
Kalyanaraman
B
B
D000154:Aconitate Hydratase / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002417:Cattle; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors* / Q000378:metabolism; D035941:Iron Regulatory Protein 1 / Q000378:metabolism; D009097:Multienzyme Complexes / Q000378:metabolism*; D009569:Nitric Oxide / Q000502:physiology*; D018384:Oxidative Stress; D046988:Proteasome Endopeptidase Complex; D011990:Receptors, Transferrin / Q000502:physiology*; D025801:Ubiquitin / Q000378:metabolism*
D009097:Multienzyme Complexes; D011990:Receptors, Transferrin; D025801:Ubiquitin; D009569:Nitric Oxide; D006861:Hydrogen Peroxide; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D000154:Aconitate Hydratase; D035941:Iron Regulatory Protein 1; D005978:Glutathione