Proteomics analysis of human umbilical vein endothelial cells treated with resveratrol

Proteomics analysis of human umbilical vein endothelial cells treated with resveratrol
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DOI:
10.1007/s00726-012-1248-4
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发表时间:
2012-02
期刊:
影响因子:
3.5
通讯作者:
B. Shao;Mei Tang;Ziqiang Li;Rui Zhou;Yaqi Deng;Chunlai Nie;Zhu Yuan;Liangxue Zhou;M. Tang;A. Tong;Yuquan Wei
B. Shao;Mei Tang;Ziqiang Li;Rui Zhou;Yaqi Deng;Chunlai Nie;Zhu Yuan;Liangxue Zhou;M. Tang;A. Tong;Yuquan Wei
中科院分区:
生物学3区
文献类型:
--
作者:
B. Shao;Mei Tang;Ziqiang Li;Rui Zhou;Yaqi Deng;Chunlai Nie;Zhu Yuan;Liangxue Zhou;M. Tang;A. Tong;Yuquan Wei

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在过去的十年中,小多酚白藜芦醇作为一种潜在的治疗或预防多种与年龄相关的慢性疾病的药物受到了广泛的关注,包括心血管动脉粥样硬化、癌症、高血压和糖尿病,但白藜芦醇诱导这些有益作用的生物学过程和分子途径,以及它的安全性和毒理学仍未明确。为探讨白藜芦醇参与改善内皮功能障碍和血管疾病的分子机制,本研究采用蛋白质组学方法(2-DE联合MS/MS)研究了白藜芦醇治疗后人脐静脉内皮细胞蛋白谱的变化。结果鉴定出4个下调蛋白种:延伸因子2 (EEF2)、羧甲基-cofilin-1 (cofilin-1)、乙酰基-真核翻译起始因子5A-1 (acetyl-EIF5A)和自整合障碍因子,以及5个上调蛋白种:热休克蛋白β -1 (HSP27)、磷酸化-HSP27、磷酸化-stathmin、烟碱-核苷酸焦磷酸化酶和1,2-二羟基-3-酮-5-甲基硫喷苯双加氧酶。其中,两个翻译相关蛋白(EEF2和acetyl-EIF5A)的变化最为显著(超过10倍)。免疫印迹实验进一步证实了Phospho-EEF2的显著上调。值得注意的是,在本研究中发现,暴露于白藜芦醇后,几种具有转录后修饰的蛋白质物种(羧甲基-,乙酰基-和磷酸基-)发生了改变。这些发现可能提高我们对白藜芦醇对内皮细胞多效作用的分子机制的理解。
In the past decade, the small polyphenol resveratrol has received widespread attention as either a potential therapy or as a preventive agent for numerous age-related chronic diseases, including cardiovascular atherosclerosis, cancer, hypertension, and diabetes, but the biological processes and molecular pathways by which resveratrol induces these beneficial effects, as well as its safety and toxicology remain largely undefined. To explore the molecular mechanisms of resveratrol involved in the amelioration of endothelial dysfunction and vascular disease, in the present study the protein profile changes of human umbilical vein endothelial cells in response to resveratrol treatment were investigated using proteomics approaches (2-DE combined with MS/MS). As a result, four down-regulated protein species named elongation factor 2 (EEF2), carboxymethyl-cofilin-1 (cofilin-1), acetyl-eukaryotic translation initiation factor 5A-1 (acetyl-EIF5A) and barrier-to-autointegration factor, and five up-regulated protein species named heat shock protein beta-1 (HSP27), phospho-HSP27, phospho-stathmin, Nicotinate-nucleotide pyrophosphorylase and 1,2-dihydroxy-3-keto-5-methylthiopentene dioxygenase were identified. Among them, two translation-related protein species (EEF2 and acetyl-EIF5A) were the most significantly changed (over tenfold). Phospho-EEF2 was further verified to be dramatically up-regulated by immunoblot assays. It is notable that in the present study several protein species with post-transcriptional modification (carboxymethyl-, acetyl-, and phospho-) were found to be altered following exposure to resveratrol. These findings may improve our understanding of the molecular mechanisms underlying the pleiotropic effects of resveratrol on endothelial cells.