Intermittent high glucose enhances ICAM-1, VICAM-1, E-selectin and interleukin-6 expression in human umbilical enclothelial cells in culture:: the role of poly(ADP-ribose) polymerase
Intermittent high glucose enhances ICAM-1, VICAM-1, E-selectin and interleukin-6 expression in human umbilical enclothelial cells in culture:: the role of poly(ADP-ribose) polymerase
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DOI：
10.1111/j.1538-7836.2004.00835.x
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发表时间：
2004-08-01
影响因子：
10.4
通讯作者：
Ceriello, A
中科院分区：
文献类型：
--
作者：
Piconi, L;Quagliaro, L;Ceriello, A
先前已经报道，暴露于恒定高浓度葡萄糖的内皮细胞上调粘附分子的表达。此外，有人认为这种现象与氧化应激的产生有关。也有人认为，与高糖相关的氧化损伤诱导酶聚ADP核糖聚合酶（PARP）的活化，这可以促进粘附分子的表达和炎症的产生。最近的体内和体外证据表明，葡萄糖的振荡可能在促进糖尿病心血管并发症的发展中发挥自主和直接的作用。在这项研究中，我们研究了持续高浓度和间歇性高浓度葡萄糖油硝基酪氨酸形成（亚硝化应激的标志物）和粘附分子（ICAM-1，VCAM-1和E-选择素）的影响，以及在人脐静脉内皮细胞中白细胞介素（IL）-6表达，无论是否存在PJ 34，PARP的有效抑制剂。我们发现，振荡葡萄糖比稳定的高糖更有效地触发硝基酪氨酸的产生和诱导粘附分子和IL-6的表达。PARP的药理学抑制抑制硝基酪氨酸形成、粘附分子表达和IL-6至正常葡萄糖条件下观察到的水平。因此，PARP活化似乎参与促进亚硝化应激和上调粘附分子和暴露于振荡高葡萄糖条件的内皮细胞中的炎症。
It has been previously reported that endothelial cells exposed to constant high concentrations of glucose upregulate the expression of adhesion molecules. Moreover, it has been suggested that this phenomenon is related to generation of oxidative stress. It has also been suggested that oxidative injuries, related to high glucose, induce the activation of the enzyme poly ADP ribose polymerase (PARP), which can promote the expression of adhesion molecules and the generation of inflammation. Recent in-vivo and in-vitro evidence suggests that oscillation of glucose may play an autonomous and direct role in favoring the development of cardiovascular complications in diabetes. In this study we have investigated the effects of constantly high and intermittently high glucose oil nitrotyrosine formation (a marker of nitrosative stress) and adhesion Molecule (ICAM-1, VCAM-1 and E-selectin), as well as on interleukin (IL)-6 expression in human umbilical vein endothelial cells, either in the presence or in the absence of PJ34, a potent inhibitor of PARP. We found that oscillating glucose was more effective in triggering the generation of nitrotyrosine and inducing the expression of adhesion molecules and IL-6 than stable high glucose. Pharmacological inhibition of PARP suppressed both nitrotyrosine formation, adhesion molecule expression and IL-6 to the levels seen in the normal glucose conditions. Thus, PARP activation appears to be involved in both promoting nitrosative stress and upregulating adhesion molecules and inflammation in endothelial cells exposed to oscillating high glucose conditions.