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微小 RNA let-7c 抑制 Bcl-xl 表达并调节氧化型低密度脂蛋白诱导的内皮细胞凋亡。

MicroRNA let-7c inhibits Bcl-xl expression and regulates ox-LDL-induced endothelial apoptosis.

机构信息

Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, PR China.

出版信息

BMB Rep. 2012 Aug;45(8):464-9. doi: 10.5483/BMBRep.2012.45.8.033.

Abstract

Endothelial cells (ECs) apoptosis induced by oxidized low-density lipoprotein (ox-LDL) is thought to play a critical role in atherosclerosis. MicroRNAs (miRNAs) are a class of noncoding RNAs that posttranscriptionally regulate the expression of genes involved in diverse cell functions, including differentiation, growth, proliferation, and apoptosis. MiRNA let-7 family is known to be involved in the regulation of cell apoptosis. However, the function of let-7 in ox-LDL induced ECs apoptosis and atherosclerosis is still unknown. Here, we show that let-7c expression was markedly up-regulated in ox-LDL induced apoptotic human umbilical cord vein endothelial cells (HUVECs). Let-7c over-expression enhanced apoptosis in ECs whereas inhibition of let-7c could partly alleviate apoptotic cell death mediated by ox-LDL. Searching for how let-7c affected apoptosis, we discovered that antiapoptotic protein Bcl-xl was a direct target of let-7c in ECs. Our data suggest that let-7c contributes to endothelial apoptosis through suppression of Bcl-xl.

摘要

氧化型低密度脂蛋白(ox-LDL)诱导的内皮细胞(ECs)凋亡被认为在动脉粥样硬化中起关键作用。microRNAs(miRNAs)是一类非编码 RNA,可在后转录水平上调节参与多种细胞功能(包括分化、生长、增殖和凋亡)的基因表达。miRNA let-7 家族被认为参与细胞凋亡的调节。然而,let-7 在 ox-LDL 诱导的 ECs 凋亡和动脉粥样硬化中的作用尚不清楚。在这里,我们发现 let-7c 在 ox-LDL 诱导的人脐静脉内皮细胞(HUVECs)凋亡中表达明显上调。let-7c 的过表达增强了 ECs 的凋亡,而抑制 let-7c 可部分减轻 ox-LDL 介导的凋亡细胞死亡。为了研究 let-7c 如何影响细胞凋亡,我们发现抗凋亡蛋白 Bcl-xl 是 ECs 中 let-7c 的直接靶标。我们的数据表明,let-7c 通过抑制 Bcl-xl 促进内皮细胞凋亡。

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