%0 Journal Article
%T Effects of epoxyeicosatrienoic acids on levels of eNOS phosphorylation and relevant signaling transduction path-ways involved<br>Effects of epoxyeicosatrienoic acids on levels of eNOS phosphorylation and relevant signaling transduction pathways involved
%A CHEN Ruijuan
%A JIANG Jiangang
%A XIAO Xiao
%A WANG Daowen
%A <br>CHEN Ruijuan
%A JIANG Jiangang
%A XIAO Xiao & WANG Daowen . The Institute of Hypertension and
%J 中国科学C辑(英文版)
%D 2005
%I Springer
%X Endothelial nitric oxide synthase (eNOS) is a key enzyme responsible for the regu-lation of vascular homeostasis. Many humor factors and mechanical forces can affect eNOS ac-tivity via phosphorylation modification but the mechanisms involved vary with stimuli applied. We have demonstrated that cytochrome P450 (CYP) epoxygenase-dependent metabolites of ara-chidonic acid, epoxyeicosatrienoic acids (EETs), can robustly up-regulate eNOS expression and its activity, however the relevant signaling pathways responsible for activity regulation are not well known. In this study, we explored the role of PI3 kinase (PI3K)/protein kinase B (Akt) sig-naling pathway in eNOS expression and its phosphorylation in response to EETs via direct addi-tion of EETs into cultured bovine aorta endothelial cells (BAECs) and recombinant adeno- asso-ciated virus-mediated transfection of CYP epoxygenase genes CYPF87V and CYP2C11 to pro-duce endogenous EETs followed by co-treatment with PI3K or Akt inhibitor. Results show that both exogenous and endogenous EETs could remarkably enhance eNOS expression and its phosphorylation at Ser1179 and Thr497 residues; PI3K inhibitor LY294002 could inhibit EETs-induced increase in eNOS-Ser(P)1179 but had no effect on the change of eNOS-Thr(P)497, while Akt inhibitor could attenuate the increase in phosphor-eNOS at both residues; both of the two inhibitors could block EETs-enhanced eNOS expression. These results lead to conclusions: (i) EETs-mediated regulation of eNOS activity may be related with the changes of phosphoryla-tion level at eNOS-Ser1179 via PI3K/Akt and eNOS-Thr497 via Akt; (ii) PI3K/Akt signaling pathway is involved in the up-regulation of eNOS expression by EETs.
%K epoxyeicosatrienoic acids
%K endothelial nitric oxide synthase (eNOS)
%K PI3 kinase
%K Protein kinase B (Akt)
%K phos-phorylation<br>
%U http://www.alljournals.cn/get_abstract_url.aspx?pcid=90BA3D13E7F3BC869AC96FB3DA594E3FE34FBF7B8BC0E591&jid=180CF3A72E750F3261A8A60EDC957784&aid=E7166DA0FD8CEE2DA915E944140F8FBF&yid=2DD7160C83D0ACED&vid=B6DA1AC076E37400&iid=94C357A881DFC066&sid=DDDA4F26E8AD3C0E&eid=42D7028D961473F8&journal_id=1674-7305&journal_name=ScienceChina.Lifesciences&referenced_num=0&reference_num=23