(-)-Epigallocatechin Gallate Suppresses Proliferation of Vascular Smooth Muscle Cells Induced by High Glucose by Inhibition of PKC and ERK1/2 Signalings
(-)-Epigallocatechin Gallate Suppresses Proliferation of Vascular Smooth Muscle Cells Induced by High Glucose by Inhibition of PKC and ERK1/2 Signalings
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(-)-表没食子儿茶素没食子酸酯通过抑制 PKC 和 ERK1/2 信号传导来抑制高血糖诱导的血管平滑肌细胞增殖
DOI：
10.1021/jf2024819
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发表时间：
2011-11-09
影响因子：
6.1
通讯作者：
Zeng, Chunyu
中科院分区：
文献类型：
--
作者：
Yang, Jian;Han, Yu;Zeng, Chunyu
血管平滑肌细胞（VSMCs）的增殖在糖尿病相关血管并发症的发生和进展中起着重要作用(-)-儿茶素（EGCG），从绿茶中提取的主要儿茶素，能够在动物模型中发挥抗糖尿病作用。本研究验证了EGCG可能对高糖诱导的VSMC增殖有抑制作用的假设。VSMC增殖是通过[H-3]-胸苷结合和3-（4,5-二甲基噻唑-2-基）-二苯基溴化四唑（MTT）摄取来测定的。细胞外信号调节激酶（ERK） 1/2磷酸化是通过免疫印迹法测定的。通过测定其底物Elk-1的磷酸化能力来检测ERK1/2的活性，葡萄糖以浓度依赖的方式增加VSMC的增殖，EGCG的存在使VSMC增殖减少，高葡萄糖（30 mM）介导的VSMC增殖参与蛋白激酶C （PKC）和ERK1/2信号传导。由于其作用被PKC抑制剂（PKC inhibitor 19-31）和ERK1/2抑制剂（PD98059）阻断，EGCG预处理VSMCs可显著抑制高糖对PKC和ERK1/2激活的刺激作用，进而抑制其下游转录因子Elk 1磷酸化。综上所述，EGCG可通过抑制VSMCs中PKC和ERK1/2信号来抑制高糖诱导的VSMC增殖。这表明EGCG可能是一种减少糖尿病血管并发症的药物
Proliferation of vascular smooth muscle cells (VSMCs) plays,an important role in the development and progression of diabetes-related vascular complications (-)-Epigallocatechin gallate, (EGCG), the Major catechin derived from green tea, is able to exert antidiabetes effects in animal models However, it is not known whether or not EGCG inhibits VSMC proliferation induced by high glucose This study tested the hypothesis that EGCG might have an inhibitory effect on VSMC proliferation induced by high glucose VSMC proliferation was determined by [H-3]-thymidine incorporation and uptake of 3-(4,5-dimethylthiazol-2-yl)-diphenyltetrazolium bromide (MTT) Extracellular signal-regulated kinase (ERK) 1/2 phosphorylation was determined by immunoblotting, and ERK 1/2 activity was detected by measuring the ability to phosphorylate its substrate Elk-1 Glucose increased VSMC proliferation in a concentration-dependent manner, which was reduced in the presence of EGCG VSMC proliferation mediated by high glucose (30 mM) was involved in protein kinase C (PKC) and ERK1/2 signalings, because its effect was blocked by PKC inhibitor (PKC inhibitor 19-31) and ERK1/2 inhibitor (PD98059) Pretreatment of VSMCs with EGCG significantly inhibited the stimulatory effect of high glucose on PKC and ERK1/2 activation, followed by attenuation of its downstream transcription factor Elk 1 phosphorylation Taken together, these results suggest that EGCG could suppress VSMC proliferation induced by high glucose by inhibition of PKC and ERK1/2 signalings in VSMCs, which indicates that EGCG might be a possible medicine to reduce vascular complications in diabetes