Rosiglitazone inhibits high glucose-induced apoptosis in human umbilical vein endothelial cells through the PI3K/Akt/eNOS pathway.
Rosiglitazone inhibits high glucose-induced apoptosis in human umbilical vein endothelial cells through the PI3K/Akt/eNOS pathway.
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DOI：
10.1139/y09-040
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发表时间：
2009-07
影响因子：
2.1
通讯作者：
Jing Wu;M. Lei;Xiao-yun Xie;Lan Liu;Yanmei She;Juan Mo;Shan Wang
中科院分区：
文献类型：
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作者：
Jing Wu;M. Lei;Xiao-yun Xie;Lan Liu;Yanmei She;Juan Mo;Shan Wang
既往研究表明，磷脂酰肌醇3-激酶/Akt/内皮型一氧化氮合酶/NO （PI3K/Akt/eNOS/NO）通路参与高糖诱导的内皮细胞凋亡，罗格列酮对内皮具有保护作用。在本研究中，我们研究了罗格列酮对高糖暴露的人脐静脉内皮细胞（HUVECs）的抗凋亡作用，并探讨其可能的机制。高糖（33 mmol/L）处理48 h显著诱导HUVECs凋亡，同时caspase-3活性升高。高糖处理也降低了Akt和eNOS磷酸化水平，并随之产生NO。罗格列酮（1微mol/L）可减弱高糖诱导的这些改变。有趣的是，罗格列酮的抗凋亡作用被PI3K抑制剂（LY294002, wortmannin）或eNOS抑制剂ng -l-硝基精氨酸甲酯（l-NAME）抑制。LY294002、wortmannin和l-NAME也分别抑制了罗格列酮对Akt和eNOS磷酸化的逆转作用。这些发现表明罗格列酮通过PI3K/Akt/eNOS途径抑制高糖诱导的HUVECs细胞凋亡。
Previous studies have shown that the phosphatidylinositol 3-kinase / Akt / endothelial nitric oxide synthase / NO (PI3K/Akt/eNOS/NO) pathway is involved in high glucose-induced endothelial cell apoptosis and rosiglitazone has a protective effect on endothelium. In the present study, we investigated the antiapoptotic effect of rosiglitazone on human umbilical vein endothelial cells (HUVECs) exposed to high glucose and explored its possible mechanism. Treatment of high glucose (33 mmol/L) for 48 h significantly induced the apoptosis of HUVECs, concomitantly with increased caspase-3 activity. High glucose treatment also decreased Akt and eNOS phosphorylation levels with subsequent NO production. All these alterations induced by high glucose were attenuated by rosiglitazone (1 micromol/L). Interestingly, the antiapoptotic effect of rosiglitazone was inhibited by PI3K inhibitor (LY294002, wortmannin) or eNOS inhibitor NG-l-nitro-arginine methyl ester (l-NAME). The reverse effects of rosiglitazone on phosphorylation of Akt and eNOS with subsequent NO production were also inhibited by LY294002, wortmannin or l-NAME, respectively. These findings suggest that rosiglitazone inhibits high glucose-induced apoptosis in HUVECs through the PI3K/Akt/eNOS pathway.