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.
Artículo
en Inglés
| WPRIM
| ID: wpr-166672
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.
Texto completo:
Disponible
Índice:
WPRIM (Pacífico Occidental)
Asunto principal:
Inhibidores de Fosfodiesterasa
/
Fosforilación
/
Tetrazoles
/
Factores de Tiempo
/
Transducción de Señal
/
Línea Celular
/
Supervivencia Celular
/
Lipopolisacáridos
/
Proteína de Unión a Elemento de Respuesta al AMP Cíclico
/
Apoptosis
Límite:
Humanos
Idioma:
Inglés
Revista:
The Korean Journal of Internal Medicine
Año:
2009
Tipo del documento:
Artículo
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