Antiangiogenic effect of rosiglitazone is mediated via peroxisome proliferator-activated receptor gamma-activated maxi-K channel opening in human umbilical vein endothelial cells.

The Journal of Biological Chemistry
Ki Young Kim, Hyae Gyeong Cheon

Abstract

Recent evidence shows that peroxisome proliferator-activated receptor gamma (PPARgamma) ligands induce the antiangiogenic effect in endothelial cells and tumors. In the present study, we elucidated the involvement of maxi-K channel activation in the antiangiogenic effect of rosiglitazone, a well known PPARgamma ligand in human umbilical vein endothelial cells. We found that the antiangiogenic effects of rosiglitazone were reversed by either bisphenol A diaglycidyl ether, a PPARgamma antagonist, or iberiotoxin, a maxi-K channel blocker. Knockdown of maxi-K channel expression also reversed the antiangiogenic effects. Iberiotoxin reversed the rosiglitazone-induced hyperpolarization while having no effect on the endogenous PPARgamma activation, suggesting that rosiglitazone activates maxi-K channel via PPARgamma. In the rosiglitazone-induced antiangiogenic process, endothelial nitric-oxide synthase-Ser1179 phosphorylation and NO production were significantly elevated, and treatment with the NOS inhibitor N(G)-monomethyl-L-arginine acetate abolished the antiangiogenic and apoptotic effects of rosiglitazone, indicating NO as a key mediator of the rosiglitazone actions. In conclusion, rosiglitazone significantly inhibited VEGF165-indu...Continue Reading

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Citations

Oct 13, 2007·Naunyn-Schmiedeberg's Archives of Pharmacology·Birgit Eichhorn, Dobromir Dobrev
Dec 9, 2008·Antioxidants & Redox Signaling·Milton HamblinY Eugene Chen
Dec 2, 2008·PPAR Research·Dorina VeliceasaOlga V Volpert
May 7, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Ke-Jie YinY Eugene Chen
Jan 11, 2014·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Peter DromparisM Sean McMurtry
Oct 12, 2011·Expert Review of Cardiovascular Therapy·Caroline Jane MagriStephen Fava
Aug 19, 2006·Expert Opinion on Investigational Drugs·Andrea GalliCalogero Surrenti
Oct 10, 2007·Expert Opinion on Investigational Drugs·Costas GiaginisStamatios Theocharis
Jul 22, 2014·Journal of Biomedical Informatics·Ning ShangTrevor Cohen
Feb 16, 2008·Circulation Research·Sheng Zhong DuanRichard M Mortensen
Aug 14, 2020·International Journal of Molecular Sciences·Nicole Wagner, Kay-Dietrich Wagner
Jun 23, 2020·Prostaglandins & Other Lipid Mediators·Anna StavniichukJohn D Imig
Apr 27, 2013·The American Journal of Pathology·Jin-Tang Dong

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