Intermittent high glucose enhances ICAM-1, VCAM-1 and E-selectin expression in human umbilical vein endothelial cells in culture: The distinct role of protein kinase C and mitochondrial. superoxide production
Intermittent high glucose enhances ICAM-1, VCAM-1 and E-selectin expression in human umbilical vein endothelial cells in culture: The distinct role of protein kinase C and mitochondrial. superoxide production
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DOI：
10.1016/j.atherosclerosis.2005.03.015
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发表时间：
2005-12-01
期刊：
影响因子：
5.3
通讯作者：
Ceriello, A
中科院分区：
文献类型：
--
作者：
Quagliaro, L;Piconi, L;Ceriello, A
在这项研究中，研究了稳定和间歇性高葡萄糖浓度对培养 HUVEC 中 ICANI-1、VCAM-1 和 E-选择素产生、PKC 活性以及 PKC β I、β II 和 8 亚型表达的影响。在稳定高糖状态下，ICAM-1、VCAM-1和E-选择素浓度以及rnRNA表达增加，并且这种作用在间歇性高糖状态下更为明显。与稳定的高葡萄糖相比，波动的葡萄糖中 PKC 活性增加，这是由于 β I、β II 和 δ 异构体的过度表达。添加总PKC抑制剂双吲哚基马来酰亚胺-I (BIMI-1)和PKCβ特异性抑制剂LY379196后，ICAM-1、VCAM-1和E-选择素同样减少。 8-羟基脱氧鸟苷 (8-OHdG) 是 DNA 氧化损伤的敏感指标，在稳定状态下增加，在间歇性高血糖下甚至更多，并且被 BIMI-I 和 LY379196 降低。然而，当添加线粒体复合物 It 的抑制剂噻吩酰三氟丙酮 (TTFA) 和 SOD 模拟物 Mn(III) 四（4-苯甲酸）氯化卟啉 (MnTBAP) 时，所有粘附分子、任何 PKC 亚型表达和 8-羟基脱氧鸟苷在常数和 振荡葡萄糖。 总之，间歇性高葡萄糖比稳定高葡萄糖诱导粘附分子更大的表达；这种效应似乎与 PKC beta 的激活有关，但完全依赖于线粒体自由基的过度产生。 (c) 2005 Elsevier Ireland Ltd. 保留所有权利。
In this study the effects of stable and intermittent high glucose concentrations on ICANI-1, VCAM-1 and E-selectin production, PKC activity and PKC beta I, beta II and 8 isoforms expression in cultured HUVEC have been examined. In stable high glucose ICAM-1, VCAM-1 and E-selectin concentration and rnRNA expression increased, and this effect was even more evident in intermittent high glucose. PKC activity increased in fluctuating glucose compared to stable high glucose, due to an over-expression of beta I, beta II and delta isoforms. ICAM-1, VCAM-1 and E-selectin, after the adding of total PKC inhibitor bisindolylmaleimide-I (BIMI-1) and LY379196, a specific inhibitor of PKC beta, were equally reduced. 8-Hydroxydeoxyguanosine (8-OHdG), a sensitive indicator of oxidative damage to DNA, increased in stable and even more in intermittent high glucose and was reduced by both BIMI-I and LY379196. However, when thenoyltrifluoroacetone (TTFA), an inhibitor of mitochondrial complex It and the SOD mimetic Mn(III)tetrakis(4-benzoic acid) porphyrin chloride (MnTBAP) were added, all adhesion molecules, any PKC isoforms expression and 8-hydroxydeoxyguanosine were normalized in both constant and oscillating glucose.In conclusion intermittent high glucose induces a greater expression of the adhesion molecules than stable high glucose; this effect seems to be related to an activation of PKC beta, but completely dependent from mitochondrial free radicals over-production. (c) 2005 Elsevier Ireland Ltd. All rights reserved.