Fenofibrate activates AMPK and increases eNOS phosphorylation in HUVEC
Fenofibrate activates AMPK and increases eNOS phosphorylation in HUVEC
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DOI：
10.1016/j.bbrc.2006.01.052
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发表时间：
2006-03-24
影响因子：
3.1
通讯作者：
Murohara, T
中科院分区：
文献类型：
--
作者：
Murakami, H;Murakami, R;Murohara, T
非诺贝特通过降脂和抗炎作用改善内皮功能。此外，非诺贝特已被证明可上调内皮型一氧化氮合酶（eNOS）。据报道，amp活化蛋白激酶（AMPK）可使eNOS Ser-1177位点磷酸化，并刺激血管内皮源性一氧化氮（NO）的产生。我们在此报告非诺贝特激活AMPK并增加人脐静脉内皮细胞（HUVEC）的eNOS磷酸化和NO生成。非诺贝特与HUVEC孵育增加了AMPK和乙酰辅酶a羧化酶的磷酸化。非诺贝特同时增加eNOS磷酸化和NO的产生。蛋白激酶A和磷脂酰肌醇3-激酶抑制剂未能抑制非诺贝特诱导的eNOS磷酸化。beazfibrate和WY-14643都没有激活HUVEC中的AMPK。此外，非诺贝特无需任何转录活性即可激活AMPK。这些结果表明，非诺贝特通过AMPK激活刺激eNOS磷酸化和NO的产生，这被认为是这种激动剂的一个新特征，与它对过氧化物酶体增殖物激活受体α的作用无关。(c) 2006爱思唯尔公司版权所有。
Fenofibrate improves endothelial function by lipid-lowering and anti-inflammatory effects. Additionally, fenofibrate has been demonstrated to upregulate endothelial nitric oxide synthase (eNOS). AMP-activated protein kinase (AMPK) has been reported to phosphorylate eNOS at Ser-1177 and stimulate vascular endothelium-derived nitric oxide (NO) production. We report here that fenofibrate activates AMPK and increases eNOS phosphorylation and NO production in human umbilical vein endothelial cells (HUVEC). Incubation of HUVEC with fenofibrate increased the phosphorylation of AMPK and acetyl-CoA carboxylase. Fenofibrate simultaneously increased eNOS phosphorylation and NO production. Inhibitors of protein kinase A and phosphatidylinositol 3-kinase failed to suppress the fenofibrate-induced eNOS phosphorylation. Neither bezafibrate nor WY-14643 activated AMPK in HUVEC. Furthermore, fenofibrate activated AMPK without requiring any transcriptional activities. These results indicate that fenofibrate stimulates eNOS phosphorylation and NO production through AMPK activation, which is suggested to be a novel characteristic of this agonist and unrelated to its effects on peroxisome proliferator-activated receptor alpha. (c) 2006 Elsevier Inc. All rights reserved.