Cilostazol Protects Endothelial Cells Against Lipopolysaccharide-Induced Apoptosis Through ERK1/2- and P38 MAPK-Dependent Pathways
The Korean Journal of Internal Medicine
; : 113-122, 2009.
Article
en En
| WPRIM
| ID: wpr-166672
Biblioteca responsable:
WPRO
ABSTRACT
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 cAMPresponsive 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 mitochondriadependent 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 cilostazolmediated protection.
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Texto completo:
1
Índice:
WPRIM
Asunto principal:
Inhibidores de Fosfodiesterasa
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Fosforilación
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Tetrazoles
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Factores de Tiempo
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Transducción de Señal
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Línea Celular
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Supervivencia Celular
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Lipopolisacáridos
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Proteína de Unión a Elemento de Respuesta al AMP Cíclico
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Apoptosis
Límite:
Humans
Idioma:
En
Revista:
The Korean Journal of Internal Medicine
Año:
2009
Tipo del documento:
Article