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
in English
| 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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Phosphodiesterase Inhibitors
/
Phosphorylation
/
Tetrazoles
/
Time Factors
/
Signal Transduction
/
Cell Line
/
Cell Survival
/
Lipopolysaccharides
/
Cyclic AMP Response Element-Binding Protein
/
Apoptosis
Limits:
Humans
Language:
English
Journal:
The Korean Journal of Internal Medicine
Year:
2009
Type:
Article
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