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HO-1 Induced by Cilostazol Protects Against TNF-alpha-associated Cytotoxicity via a PPAR-gamma-dependent Pathway in Human Endothelial Cells
The Korean Journal of Physiology and Pharmacology ; : 83-88, 2011.
Artigo em Inglês | WPRIM | ID: wpr-727374
ABSTRACT
A large body of evidence has indicated that induction of endogenous antioxidative proteins seems to be a reasonable strategy for delaying the progression of cell injury. In our previous study, cilostazol was found to increase the expression of the antioxidant enzyme heme oxygenase-1 (HO-1) in synovial cells. Thus, the present study was undertaken to examine whether cilostazol is able to counteract tumor necrosis factor-alpha (TNF-alpha)-induced cell death in endothelial cells via the induction of HO-1 expression. We exposed human umbilical vein endothelial cells (HUVECs) to TNF-alpha (50 ng/ml), with or without cilostazol (10 microM). Pretreatment with cilostazol markedly reduced TNF-alpha-induced viability loss in the HUVECs, which was reversed by zinc protoporphyrine IX (ZnPP), an inhibitor of HO-1. Moreover, cilostazol increased HO-1 protein and mRNA expression. Cilostazol-induced HO-1 induction was markedly attenuated not only by ZnPP but also by copper-protoporphyrin IX (CuPP). In an assay measuring peroxisome proliferator-activated receptor-gamma (PPAR-gamma) transcription activity, cilostazol directly increased PPAR-gamma transcriptional activity which was completely abolished by HO-1 inhibitor. Furthermore, increased PPAR-gamma activity by cilostazol and rosiglitazone was completely abolished in cells transfected with HO-1 siRNA. Taken together, these results indicate that cilostazol up-regulates HO-1 and protects cells against TNF-alpha-induced endothelial cytotoxicity via a PPAR-gamma-dependent pathway.
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Texto completo: DisponíveL Índice: WPRIM (Pacífico Ocidental) Assunto principal: Tetrazóis / Zinco / RNA Mensageiro / Proteínas / Fator de Necrose Tumoral alfa / Morte Celular / Peroxissomos / RNA Interferente Pequeno / Células Endoteliais / Tiazolidinedionas Limite: Humanos Idioma: Inglês Revista: The Korean Journal of Physiology and Pharmacology Ano de publicação: 2011 Tipo de documento: Artigo

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Texto completo: DisponíveL Índice: WPRIM (Pacífico Ocidental) Assunto principal: Tetrazóis / Zinco / RNA Mensageiro / Proteínas / Fator de Necrose Tumoral alfa / Morte Celular / Peroxissomos / RNA Interferente Pequeno / Células Endoteliais / Tiazolidinedionas Limite: Humanos Idioma: Inglês Revista: The Korean Journal of Physiology and Pharmacology Ano de publicação: 2011 Tipo de documento: Artigo