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

Parishin from Gastrodia elata Extends the Lifespan of Yeast via Regulation of Sir2/Uth1/TOR Signaling Pathway.
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DOI:
10.1155/2016/4074690
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发表时间:
2016
影响因子:
--
通讯作者:
Qi J
Qi J
中科院分区:
生物学2区
文献类型:
--
作者:
Lin Y;Sun Y;Weng Y;Matsuura A;Xiang L;Qi J

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天麻素是从天麻中分离得到的一种酚型糖苷,是一种重要的中草药,在3、10和30 μM时可显著延长K6001酵母的复制寿命。为了阐明其作用机制,对其抗氧化性、超氧化物歧化酶活性、丙二醛和活性氧自由基进行了检测,并对SO1、Sod2、uth1和skn7酵母突变株的复制寿命进行了实时定量聚合酶链式反应分析。在氧化应激条件下,大黄素处理组的细胞存活率显著增加。正常条件下处理后,沉默信息调节因子2(Sir2)基因表达和超氧化物歧化酶活性显著增加。同时,酵母中的ROS和丙二醛水平也显著降低。K6001酵母突变株Sod1、Sod2、uth1和skn7的复制寿命不受Parishin的影响。我们还发现,在雷帕霉素(TOR)信号通路的靶点,Parishin可以降低TORC1、核糖体蛋白S26A(RPS26A)和核糖体蛋白L9A(RPL9A)的基因表达。Uth1和uth1、sir2双突变株的RPS26A和RPL9A基因表达水平均显著低于对照组。此外,K6001酵母uth1突变株中TORC1基因的表达受到显著抑制。这些结果提示,Parishin可能通过调节Sir2/Uth1/Tor信号通路发挥抗衰老作用。
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.