Protective Effects of EPA and Deleterious Effects of DHA on eNOS Activity in Ea hy 926 Cultured with Lysophosphatidylcholine
Protective Effects of EPA and Deleterious Effects of DHA on eNOS Activity in Ea hy 926 Cultured with Lysophosphatidylcholine
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DOI：
10.1007/s11745-009-3284-8
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发表时间：
2009-03-01
期刊：
影响因子：
1.9
通讯作者：
Lacour, Bernard
中科院分区：
文献类型：
--
作者：
Tardivel, Sylviane;Gousset-Dupont, Aurelie;Lacour, Bernard
氧化低密度脂蛋白(Ox-LDL)是动脉粥样硬化的危险因素，溶血磷脂酰胆碱(LysoPtdCho)被认为是Ox-LDL的主要致动脉粥样硬化成分之一。本工作的目的是比较两种膜n-3长链多不饱和脂肪酸(n-3PUFAs)EPA(二十碳五烯酸)和DHA(二十二碳六烯酸)与n-6PUFA(花生四烯酸)对组胺激活Ea-926内皮细胞内皮型一氧化氮合酶(ENOS)的影响。DHA(50 MU M)在细胞内产生ROS诱导，加重LysoPtdCho诱导的氧化应激。它不改变eNOS的基础活性，但减弱组胺对eNOS的刺激作用，不能纠正LysoPtdCho对组胺刺激的eNOS活性或Ser 1177的磷酸化的有害影响。相反，EPA(90 MU M)不改变存在或不存在LysoPtdCho时产生的ROS水平或基础eNOS活性以及组胺对eNOS的刺激作用。但可减弱LysoPtdCho和组胺刺激的eNOS活性对eNOS Ser 1177磷酸化的有害影响。EPA而不是DHA对EA HY 926中内皮细胞eNOS活性的有利作用也可能部分是由于EPA处理的细胞膜DHA含量略有下降。因此，eNOS产生的NO和氧化应激引起的ROS之间的平衡可以部分解释EPA在心血管疾病发展中的有利作用。相反，在基础状态或组胺刺激后，ARA和n-6多不饱和脂肪酸对ROS的产生或eNOS活性没有任何影响。应该进行体内实验来证实这些结果。
Oxidized low density lipoprotein (Ox-LDL) is a well-established risk factor in atherosclerosis and lysophosphatidylcholine (LysoPtdCho) is considered to be one of the major atherogenic component of Ox-LDL. The purpose of this work was to investigate the effects of two membrane n-3 long chain polyunsaturated fatty acids (n-3 PUFAs), EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) compared to n-6 PUFA, ARA (arachidonic acid), on the activation of endothelial NO synthase (eNOS) by histamine in Ea hy 926 endothelial cells incubated during 24 h in the presence or the absence of LysoPtdCho. DHA (50 mu M) produced a ROS induction in cells and aggravated the LysoPtdCho-induced oxidative stress. It did not modify the basal eNOS activity but impaired the stimulation of eNOS induced by histamine and was unable to correct the deleterious effect of LysoPtdCho on histamine-stimulated eNOS activity or phosphorylation of Ser 1177. In contrast, EPA (90 mu M) did not modify the ROS level produced in the presence or absence of LysoPtdCho or basal eNOS activity and the stimulating effect of histamine on eNOS. However, it diminished the deleterious effect of LysoPtdCho as well as on the histamine-stimulated eNOS activity on the phosphorylation on Ser 1177 of eNOS. The beneficial effect of EPA but not DHA on endothelial eNOS activity in Ea hy 926 could be also partially due to a slight decrease in membrane DHA content in EPA-treated cells. Consequently, the equilibrium between NO generated by eNOS and ROS due to oxidative stress could explain, in part, the beneficial effect of EPA on the development of cardiovascular diseases. By contrast ARA an n-6 PUFA was devoid of any effect on ROS generation or eNOS activity in the basal state or after histamine-induced stimulation. In vivo experiments should be undertaken to confirm these results.