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Cilostazol Protects Endothelial Cells Against Lipopolysaccharide-Induced Apoptosis Through ERK1/2- and P38 MAPK-Dependent Pathways

BACKGROUND/AIMS: We examined the effects of cilostazol on mitogen-activated protein kinase (MAPK) activity and its relationship with cilostazol-mediated protection against apoptosis in lipopolysaccharide (LPS)-treated endothelial cells. METHODS: Human umbilical vein endothelial cells (HUVECs) were e...

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Detalles Bibliográficos
Autores principales: Lim, Jong-Hoon, Woo, Jae-Suk, Shin, Yung-Woo
Formato: Texto
Lenguaje:English
Publicado: The Korean Association of Internal Medicine 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2698619/
https://www.ncbi.nlm.nih.gov/pubmed/19543489
http://dx.doi.org/10.3904/kjim.2009.24.2.113
Descripción
Sumario:BACKGROUND/AIMS: We examined the effects of cilostazol on mitogen-activated protein kinase (MAPK) activity and its relationship with cilostazol-mediated protection against apoptosis in lipopolysaccharide (LPS)-treated endothelial cells. METHODS: Human umbilical vein endothelial cells (HUVECs) were exposed to LPS and cilostazol with and without specific inhibitors of MAPKs; changes in MAPK activity in association with cell viability and apoptotic signaling were investigated. RESULTS: Cilostazol protected HUVECs against LPS-induced apoptosis by suppressing the mitochondrial permeability transition, cytosolic release of cytochrome c, and subsequent activation of caspases, stimulating extracellullar signal-regulated kinase (ERK1/2) and p38 MAPK signaling, and increasing phosphorylated cAMP-responsive element-binding protein (CREB) and Bcl-2 expression, while suppressing Bax expression. These cilostazol-mediated cellular events were effectively blocked by MAPK/ERK kinase (MEK1/2) and p38 MAPK inhibitors. CONCLUSIONS: Cilostazol protects HUVECs against LPS-induced apoptosis by suppressing mitochondria-dependent apoptotic signaling. Activation of ERK1/2 and p38 MAPKs, and subsequent stimulation of CREB phosphorylation and Bcl-2 expression, may be responsible for the cellular signaling mechanism of cilostazol-mediated protection.