The thiazolidinedione drug troglitazone up-regulates nitric oxide synthase expression in vascular endothelial cells
The thiazolidinedione drug troglitazone up-regulates nitric oxide synthase expression in vascular endothelial cells
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DOI：
10.1016/j.jdiacomp.2005.08.003
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发表时间：
2006-09-01
影响因子：
3
通讯作者：
Kasayama, Soji
中科院分区：
文献类型：
--
作者：
Goya, Kayoko;Sumitani, Satoru;Kasayama, Soji
内皮功能障碍是糖尿病患者常见的现象，是糖尿病血管并发症的原因之一。内皮源性一氧化氮（NO）负责血管舒张，并且在糖尿病患者中NO依赖性血管舒张减少。在本研究中，我们评估了噻唑烷二酮类（TZDs），抗糖尿病药物，已知改善胰岛素抵抗和血管舒张特性，对内皮NO合酶（eNOS）在培养的血管内皮细胞表达的影响。用TZDs曲格列酮和吡格列酮或过氧化物酶体增殖物激活受体（PPAR）γ激活剂15-脱氧-δ（12，14）-前列腺素J（2）（15-dPGJ 2）处理人脐静脉内皮细胞。Western blot和北方印迹分析eNOS蛋白和mRNA的表达。还检查了与曲格列酮具有结构相似性的α-生育酚的作用。曲格列酮上调eNOS蛋白及其mRNA水平，而吡格列酮和15-dPGJ 2未能增加其水平。与此相反，α-生育酚也增加eNOS蛋白和mRNA。这些结果表明，曲格列酮上调eNOS的表达可能通过其6-羟基苯并二氢吡喃结构，但不激活过氧化物酶体增殖物激活受体γ。(c)2006爱思唯尔公司All rights reserved.
Endothelial dysfunction is a phenomenon often observed in diabetic patients, which is a cause for vascular complications of diabetes mellitus. Endothelium-derived nitric oxide (NO) is responsible for vasodilatation, and NO-dependent vasodilatation is diminished in diabetic patients. In the present study, we evaluated the effects of thiazolidinediones (TZDs), antidiabetic drugs known to improve insulin resistance and to have vasodilating properties, on endothelial NO synthase (eNOS) expression in cultured vascular endothelial cells. Human umbilical vein endothelial cells were treated with the TZDs troglitazone and pioglitazone, or the peroxisome proliferator-activated receptor (PPAR) gamma activator 15-deoxy-Delta(12,14)-prostaglandin J(2) (15-dPGJ2). The expression of eNOS protein and its mRNA was determined by Western and Northern blot analyses, respectively. The effect of alpha-tocopherol that possesses structural similarity to troglitazone was also examined. Troglitazone up-regulated eNOS protein and its mRNA levels, whereas pioglitazone and 15-dPGJ2 failed to increase their levels. By contrast, a-tocopherol also increased in eNOS protein and mRNA. These results suggest that troglitazone up-regulates eNOS expression probably through its 6-hydroxychromanes structure but not activating PPAR gamma. (c) 2006 Elsevier Inc. All rights reserved.