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天麻素通过调控Sir2/Uth1/TOR信号通路延长酵母寿命。

Parishin from Gastrodia elata Extends the Lifespan of Yeast via Regulation of Sir2/Uth1/TOR Signaling Pathway.

作者信息

Lin Yanfei, Sun Yujuan, Weng Yufang, Matsuura Akira, Xiang Lan, Qi Jianhua

机构信息

College of Pharmaceutical Sciences, Zhejiang University, 866 Yu Hang Tang Road, Hangzhou, China.

Department of Nanobiology, Graduate School of Advanced Integration Science, Chiba University, Chiba 263-8522, Japan.

出版信息

Oxid Med Cell Longev. 2016;2016:4074690. doi: 10.1155/2016/4074690. Epub 2016 Jun 27.

Abstract

Parishin is a phenolic glucoside isolated from Gastrodia elata, which is an important traditional Chinese medicine; this glucoside significantly extended the replicative lifespan of K6001 yeast at 3, 10, and 30 μM. To clarify its mechanism of action, assessment of oxidative stress resistance, superoxide dismutase (SOD) activity, malondialdehyde (MDA), and reactive oxygen species (ROS) assays, replicative lifespans of sod1, sod2, uth1, and skn7 yeast mutants, and real-time quantitative PCR (RT-PCR) analysis were conducted. The significant increase of cell survival rate in oxidative stress condition was observed in parishin-treated groups. Silent information regulator 2 (Sir2) gene expression and SOD activity were significantly increased after treating parishin in normal condition. Meanwhile, the levels of ROS and MDA in yeast were significantly decreased. The replicative lifespans of sod1, sod2, uth1, and skn7 mutants of K6001 yeast were not affected by parishin. We also found that parishin could decrease the gene expression of TORC1, ribosomal protein S26A (RPS26A), and ribosomal protein L9A (RPL9A) in the target of rapamycin (TOR) signaling pathway. Gene expression levels of RPS26A and RPL9A in uth1, as well as in uth1, sir2 double mutants, were significantly lower than those of the control group. Besides, TORC1 gene expression in uth1 mutant of K6001 yeast was inhibited significantly. These results suggested that parishin exhibited antiaging effects via regulation of Sir2/Uth1/TOR signaling pathway.

摘要

天麻苷是从重要的传统中药天麻中分离得到的一种酚苷;该苷在3、10和30 μM浓度下能显著延长K6001酵母的复制寿命。为阐明其作用机制,进行了抗氧化应激能力评估、超氧化物歧化酶(SOD)活性、丙二醛(MDA)和活性氧(ROS)检测、sod1、sod2、uth1和skn7酵母突变体的复制寿命测定以及实时定量PCR(RT-PCR)分析。在天麻苷处理组中,观察到氧化应激条件下细胞存活率显著提高。在正常条件下用天麻苷处理后,沉默信息调节因子2(Sir2)基因表达和SOD活性显著增加。同时,酵母中的ROS和MDA水平显著降低。K6001酵母的sod1、sod2、uth1和skn7突变体的复制寿命不受天麻苷影响。我们还发现天麻苷可降低雷帕霉素靶蛋白(TOR)信号通路中TORC1、核糖体蛋白S26A(RPS26A)和核糖体蛋白L9A(RPL9A)的基因表达。uth1以及uth1、sir2双突变体中RPS26A和RPL9A的基因表达水平显著低于对照组。此外,K6001酵母uth1突变体中的TORC1基因表达受到显著抑制。这些结果表明天麻苷通过调节Sir2/Uth1/TOR信号通路发挥抗衰老作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a64d/4939362/67278e2e199b/OMCL2016-4074690.001.jpg

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