Inhibition of mammalian S6 kinase by resveratrol suppresses autophagy.
Inhibition of mammalian S6 kinase by resveratrol suppresses autophagy.
复制标题
DOI：
10.18632/aging.100056
复制
发表时间：
2009-06-03
期刊：
影响因子：
--
通讯作者：
Sinclair DA
中科院分区：
文献类型：
--
作者：
Armour SM;Baur JA;Hsieh SN;Land-Bracha A;Thomas SM;Sinclair DA
白藜芦醇是一种植物来源的多酚，可促进啮齿动物模型的健康和抗病能力，并延长低等生物的寿命。一个主要的挑战是了解白藜芦醇诱导这些有益作用的生物学过程和分子途径。自噬是细胞翻转受损成分并维持生物能量需求的关键过程。破坏亲和抗自噬信号之间的正常平衡与癌症、肝病和神经退行性疾病有关。在这里，我们表明，白藜芦醇减弱自噬响应营养限制或雷帕霉素在多个细胞系通过一个独立的途径的一个已知的目标，SIRT1。在大规模的体外激酶筛选中，我们确定p70 S6激酶（S6K1）为白藜芦醇的靶点。通过表达显性负突变体或RNA干扰来阻断S6K1活性足以破坏自噬，其程度与白藜芦醇相似。此外，白藜芦醇与S6K1敲低的共同施用不产生累加效应。这些数据表明，S6K1对于哺乳动物中自噬的完全诱导是重要的，并提高了白藜芦醇的一些有益作用是由于S6K1活性调节的可能性。
Resveratrol is a plant-derived polyphenol that promotes health and disease resistance in rodent models, and extends lifespan in lower organisms. A major challenge is to understand the biological processes and molecular pathways by which resveratrol induces these beneficial effects. Autophagy is a critical process by which cells turn over damaged components and maintain bioenergetic requirements. Disruption of the normal balance between pro- and anti-autophagic signals is linked to cancer, liver disease, and neurodegenerative disorders. Here we show that resveratrol attenuates autophagy in response to nutrient limitation or rapamycin in multiple cell lines through a pathway independent of a known target, SIRT1. In a large-scalein vitro kinase screen we identified p70 S6 kinase (S6K1) as a target of resveratrol. Blocking S6K1 activity by expression of a dominant-negative mutant or RNA interference is sufficient to disrupt autophagy to a similar extent as resveratrol. Furthermore, co-administration of resveratrol with S6K1 knockdown does not produce an additive effect. These data indicate that S6K1 is important for the full induction of autophagy in mammals and raise the possibility that some of the beneficial effects of resveratrol are due to modulation of S6K1 activity.
登录
查看更多内容
DOI：
10.1083/jcb.200707154
发表时间：
2008-01-14
期刊：
The Journal of cell biology
影响因子：
--
作者：
Madia F;Gattazzo C;Wei M;Fabrizio P;Burhans WC;Weinberger M;Galbani A;Smith JR;Nguyen C;Huey S;Comai L;Longo VD
通讯作者：
Longo VD
影响因子：
9.2
作者：
Kapahi, P;Zid, BM;Benzer, S
通讯作者：
Benzer, S
影响因子：
4.8
作者：
Noda, T;Ohsumi, Y
通讯作者：
Ohsumi, Y
影响因子：
5.5
作者：
Mieulet, Virginie;Roceri, Mila;Pende, Mario
通讯作者：
Pende, Mario
影响因子：
11.2
作者：
Opipari, AW;Tan, LJ;Liu, JR
通讯作者：
Liu, JR