Cytochrome P-450 epoxygenases protect endothelial cells from apoptosis   induced by tumor necrosis factor-alpha via MAPK and PI3K/Akt signaling   pathways

doi:10.1152/ajpheart.00783.2006

CORC > 北京大学 > 生命科学学院

	Cytochrome P-450 epoxygenases protect endothelial cells from apoptosis induced by tumor necrosis factor-alpha via MAPK and PI3K/Akt signaling pathways
	Yang, Shilin ; Lin, Li ; Chen, Ji-Xiong ; Lee, Craig R. ; Seubert, John M. ; Wang, Yan ; Wang, Hong ; Chao, Zhong-Ren ; Tao, De-Ding ; Gong, Jian-Ping ; Lu, Zai-Ying ; Wang, Dao Wen ; Zeldin, Darryl C.
刊名	american journal of physiology heart and circulatory physiology
	2007
关键词	epoxyeicosatrienoic acid arachidonic acid ARACHIDONIC-ACID METABOLISM NITRIC-OXIDE EPOXYEICOSATRIENOIC ACIDS TYROSINE PHOSPHORYLATION HYPERPOLARIZING FACTOR INHIBITS APOPTOSIS SMOOTH-MUSCLE GROWTH-FACTOR UP-REGULATION KINASE
DOI	10.1152/ajpheart.00783.2006
英文摘要	Endothelial cells play a vital role in the maintenance of cardiovascular homeostasis. Epoxyeicosatrienoic acids (EETs), cytochrome P-450 (CYP) epoxygenase metabolites of arachidonic acid in endothelial cells, possess potent and diverse biological effects within the vasculature. We evaluated the effects of overexpression of CYP epoxygenases on tumor necrosis factor-alpha (TNF-alpha)-induced apoptosis in bovine aortic endothelial cells. CYP epoxygenase overexpression significantly increased endothelial cell viability and inhibited TNF-alpha induction of endothelial cell apoptosis as evaluated by morphological analysis of nuclear condensation, DNA laddering, and fluorescent-activated cell sorting ( FACS) analysis. CYP epoxygenase overexpression also significantly inhibited caspase-3 activity and downregulation of Bcl-2 expression induced by TNF-alpha. The antiapoptotic effects of CYP epoxygenase overexpression were significantly attenuated by inhibition of the phosphatidylinositol 3-kinase (PI3K)/Akt and MAPK signaling pathways; however, inhibition of endothelial nitric oxide synthase activity had no effect. Furthermore, CYP epoxygenase overexpression significantly attenuated the extent of TNF-alpha-induced ERK1/2 dephosphorylation in a time-dependent manner and significantly increased PI3K expression and Akt phosphorylation in both the presence and absence of TNF-alpha. Collectively, these results suggest that CYP epoxygenase overexpression, which is known to increase EET biosynthesis, significantly protects endothelial cells from apoptosis induced by TNF-alpha. This effect is mediated, at least in part, through inhibition of ERK dephosphorylation and activation of PI3K/Akt signaling.; Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease; SCI(E); 70; ARTICLE; 1; H142-H151; 293
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/401394]
专题	生命科学学院
推荐引用方式 GB/T 7714	Yang, Shilin,Lin, Li,Chen, Ji-Xiong,et al. Cytochrome P-450 epoxygenases protect endothelial cells from apoptosis induced by tumor necrosis factor-alpha via MAPK and PI3K/Akt signaling pathways[J]. american journal of physiology heart and circulatory physiology,2007.
APA	Yang, Shilin.,Lin, Li.,Chen, Ji-Xiong.,Lee, Craig R..,Seubert, John M..,...&Zeldin, Darryl C..(2007).Cytochrome P-450 epoxygenases protect endothelial cells from apoptosis induced by tumor necrosis factor-alpha via MAPK and PI3K/Akt signaling pathways.american journal of physiology heart and circulatory physiology.
MLA	Yang, Shilin,et al."Cytochrome P-450 epoxygenases protect endothelial cells from apoptosis induced by tumor necrosis factor-alpha via MAPK and PI3K/Akt signaling pathways".american journal of physiology heart and circulatory physiology (2007).