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硫化氢通过激活 SIRT1 预防 H₂O₂ 诱导的人脐静脉内皮细胞衰老。

Hydrogen sulfide prevents H₂O₂-induced senescence in human umbilical vein endothelial cells through SIRT1 activation.

机构信息

Institute of Cardiovascular Disease and Key Laboratory for Arteriosclerology of Hunan Province, University of South China, Hengyang, Hunan 421001, P.R. China.

出版信息

Mol Med Rep. 2013 Jun;7(6):1865-70. doi: 10.3892/mmr.2013.1417. Epub 2013 Apr 9.

Abstract

The aim of the present study was to investigate the attenuation of endothelial cell senescence by H2S and to explore the mechanisms underlying the anti-aging effects of H2S. Senescence was induced in human umbilical vein endothelial cells (HUVECs) by incubation in 25 µmol/l H2O2 for 1 h. Senescence-associated β-galactosidase (SA-β-gal) activity was examined to determine the effects of H2S on senescent HUVECs. The results indicated that SA-β-gal activity in the H2O2-treated HUVECs was 11.2 ± 1.06%, which was attenuated in the NaHS group. Pretreatment with nicotinamide (NAM), a sirtuin 1 (SIRT1) inhibitor, inhibited the reduction in senescence associated with H2S. Immunoblot analyses revealed that SIRT1 levels in senescent HUVECs treated with NaHS (60 µM) were indistinguishable from controls; however, analyses of SIRT1 activity indicated that SIRT1 enzyme activity was enhanced. In addition, we found that H2S improves the function of senescent HUVECs. The present study demonstrated that H2S protects against HUVEC senescence, potentially through modulation of SIRT1 activity. Furthermore, this study establishes a novel endothelial protective effect of H2S.

摘要

本研究旨在探讨 H2S 对内皮细胞衰老的抑制作用,并探讨 H2S 抗衰老作用的机制。通过将人脐静脉内皮细胞(HUVEC)在 25µmol/l H2O2 中孵育 1 小时来诱导衰老。通过检测衰老相关β-半乳糖苷酶(SA-β-gal)活性来确定 H2S 对衰老 HUVEC 的影响。结果表明,H2O2 处理的 HUVEC 中 SA-β-gal 活性为 11.2±1.06%,而在 NaHS 组中则减弱。烟酰胺(NAM)预处理,一种沉默信息调节因子 1(SIRT1)抑制剂,抑制了与 H2S 相关的衰老减少。免疫印迹分析表明,用 60µM NaHS 处理的衰老 HUVEC 中的 SIRT1 水平与对照组无明显差异;然而,SIRT1 活性分析表明 SIRT1 酶活性增强。此外,我们发现 H2S 改善了衰老 HUVEC 的功能。本研究表明,H2S 可防止 HUVEC 衰老,可能通过调节 SIRT1 活性。此外,本研究确立了 H2S 的一种新的内皮保护作用。

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