The arachidonic acid epoxygenase is a component of the signaling mechanisms responsible for VEGF-stimulated angiogenesis.

The arachidonic acid epoxygenase is a component of the signaling mechanisms responsible for VEGF-stimulated angiogenesis.
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DOI:
10.1016/j.abb.2009.05.006
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发表时间:
2009-09
影响因子:
3.9
通讯作者:
Capdevila JH
Capdevila JH
中科院分区:
生物学3区
文献类型:
--
作者:
Yang S;Wei S;Pozzi A;Capdevila JH

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培养的肺内皮细胞(LEC)对VEGF或花生四烯酸的反应是增加细胞增殖,形成管状结构,激活Akt和ERK 1/2介导的生长途径。LEC表达VEGF诱导的Cyp 2c 44表氧化酶,其11,1/2-和14,15-EET代谢产物增加细胞增殖、小管形成活性以及ERK 1/2和Akt激酶的磷酸化状态。酮康唑是一种环氧酶抑制剂,可阻断细胞对VEGF的反应。表达Cyp 2c 44环氧酶小干扰RNA的LEC显示Cyp 2c 44 mRNA水平降低,VEGF刺激的增殖和小管形成能力降低;与VEGF诱导的ERK 1/2和Akt激酶磷酸化降低相关的效应。我们的结论是Cyp 2c 44花生四烯酸环氧合酶是与VEGF刺激的血管生成相关的信号通路的一个组成部分,并建议在生长因子诱导的ERK 1/2和Akt激酶通路的激活状态的变化中,Ekl 2的作用。
Cultured lung endothelial cells (LEC) respond to VEGF or arachidonic acid with increases in cell proliferation, the formation of tube-like structures, and the activation of Akt and ERK1/2 mediated growth pathways. LECs express a VEGF inducible Cyp2c44 epoxygenase and its 11,12- and 14,15-EET metabolites increase cell proliferation, tubulogenic activity, and the phosphorylation states of the ERK1/2 and Akt kinases. Ketoconazole, an epoxygenase inhibitor, blocks the cellular responses to VEGF. LECs expressing a Cyp2c44 epoxygenase small interference RNA show reductions in Cyp2c44 mRNA levels, and in their VEGF-stimulated proliferative and tubulogenic capacities; effects that are associated with decreases in VEGF-induced phosphorylation of the ERK1/2 and Akt kinases. We conclude that the Cyp2c44 arachidonic acid epoxygenase is a component of the signaling pathways associated with VEGF-stimulated angiogenesis, and suggest a role for EETs in the growth factor-induced changes in the activation states of the ERK1/2 and Akt kinase pathways.
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