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首页> 外文期刊>International Journal of Molecular Sciences >Global Gene Expression Profiling Reveals Functional Importance of Sirt2 in Endothelial Cells under Oxidative Stress
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Global Gene Expression Profiling Reveals Functional Importance of Sirt2 in Endothelial Cells under Oxidative Stress

机译:全球基因表达谱揭示了氧化应激下内皮细胞中Sirt2的功能重要性。

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The NAD+-dependent deacetylases Sirt1 and Sirt2 mediate cellular stress responses and are highly expressed in vascular endothelial cells. In contrast to the well-documented protective actions of Sirt1, the role of endothelial Sirt2 remains unknown. Using cDNA microarray and PCR validation, we examined global gene expression changes in response to Sirt2 knock down in primary human umbilical vein endothelial cells under oxidative stress. We found that Sirt2 knock down changed expression of 340 genes, which are mainly involved in cellular processes including actin binding, cellular amino acid metabolic process, transmembrane receptor protein serine/threonine kinase signaling, ferrous iron transport, protein transport and localization, cell morphogenesis, and functions associated with endosome membrane and the trans-Golgi network. These genes and associated functions were largely non-overlapping with those altered by Sirt1 knock down. Moreover, we showed that pharmacological inhibition of Sirt2 attenuated oxidant-induced cell toxicity in endothelial cells. These suggest that Sirt2 is functionally important in endothelial cells under oxidative stress, and may have a primarily distinct role as compared to Sirt1. Our results may provide a basis for future studies aiming to dissect the specific signaling pathway(s) that mediates specific Sirt2 functions in endothelial cells.
机译:NAD + 依赖的脱乙酰基酶Sirt1和Sirt2介导细胞应激反应,并在血管内皮细胞中高表达。与Sirt1的有据可查的保护作用相反,内皮Sirt2的作用仍然未知。使用cDNA微阵列和PCR验证,我们检查了在氧化应激下人类原发性脐静脉内皮细胞对Sirt2敲低反应的总体基因表达变化。我们发现Sirt2敲低了340个基因的表达变化,这些基因主要参与细胞过程,包括肌动蛋白结合,细胞氨基酸代谢过程,跨膜受体蛋白丝氨酸/苏氨酸激酶信号传导,亚铁运输,蛋白质运输和定位,细胞形态发生,和与内体膜和反高尔基网络有关的功能。这些基因和相关功能与Sirt1敲除改变后的基因基本不重叠。此外,我们表明,Sirt2的药理抑制作用减弱了内皮细胞中氧化剂诱导的细胞毒性。这些提示Sirt2在氧化应激下在内皮细胞中功能上重要,并且与Sirt1相比可能具有主要不同的作用。我们的结果可能为将来的研究提供基础,这些研究旨在剖析介导内皮细胞中特定Sirt2功能的特定信号通路。

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