Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/71518
標題: Ellagic acid protects endothelial cells from oxidized low-density lipoprotein-induced apoptosis by modulating the PI3K/Akt/eNOS pathway
作者: Ou, H.C.
Lee, W.J.
Lee, S.D.
Huang, C.Y.
Chiu, T.H.
Tsai, K.L.
Hsu, W.C.
Sheu, W.H.H.
關鍵字: Ellagic acid
Endothelium
Apoptosis
ROS
oxLDL
Akt
nitric-oxide synthase
laser-scanning cytometry
ldl-induced apoptosis
nf-kappa-b
oxidative stress
antioxidant
metabolism
activation
inhibition
expression
期刊/報告no:: Toxicology and Applied Pharmacology, Volume 248, Issue 2, Page(s) 134-143.
摘要: Endothelial apoptosis is a driving force in atherosclerosis development. Oxidized low-density lipoprotein (oxLDL) promotes inflammatory and thrombotic processes and is highly atherogenic, as it stimulates macrophage cholesterol accumulation and foam cell formation. Previous studies have shown that the phosphatidylinositol 3-kinase/Akt/endothelial nitric oxide synthase/nitric oxide (PI3K/Akt/eNOS/NO) pathway is involved in oxLDL-induced endothelial apoptosis. Ellagic acid, a natural polyphenol found in berries and nuts, has in recent years been the subject of intense research within the fields of cancer and inflammation. However, its protective effects against oxLDL-induced injury in vascular endothelial cells have not been clarified. In the present study, we investigated the anti-apoptotic effect of ellagic acid in human umbilical vein endothelial cells (HUVECs) exposed to oxLDL and explored the possible mechanisms. Our results showed that pretreatment with ellagic acid (5-20 mu M) significantly attenuated oxLDL-induced cytotoxicity, apoptotic features, and generation of reactive oxygen species (ROS). In addition, the antiapoptotic effect of ellagic acid was partially inhibited by a PI3K inhibitor (wortmannin) and a specific eNOS inhibitor (cavtratin) but not by an ERK inhibitor (PD98059). In exploring the underlying mechanisms of ellagic acid action, we found that oxLDL decreased Akt and eNOS phosphorylation, which in turn activated NF-kappa B and downstream pro-apoptotic signaling events including calcium accumulation, destabilization of mitochondrial permeability, and disruption of the balance between pro- and anti-apoptotic Bcl-2 proteins. Those alterations induced by oxLDL, however, were attenuated by pretreatment with ellagic acid. The inhibition of oxLDL-induced endothelial apoptosis by ellagic acid is due at least in part to its anti-oxidant activity and its ability to modulate the PI3K/Akt/eNOS signaling pathway. (C) 2010 Elsevier Inc. All rights reserved.
URI: http://hdl.handle.net/11455/71518
ISSN: 0041-008X
文章連結: http://dx.doi.org/10.1016/j.taap.2010.07.025
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