AMP-activated protein kinase inhibits NF-κB signaling and inflammation: impact on healthspan and lifespan.
AMP-activated protein kinase inhibits NF-κB signaling and inflammation: impact on healthspan and lifespan.
复制标题
AMP激活的蛋白激酶抑制NF-κB信号传导和炎症：对健康范围和寿命的影响。
DOI：
10.1007/s00109-011-0748-0
复制
发表时间：
2011-07
影响因子：
4.7
通讯作者：
Kaarniranta, Kai
中科院分区：
文献类型：
--
作者：
Salminen, Antero;Hyttinen, Juha M. T.;Kaarniranta, Kai
腺苷一磷酸活化蛋白激酶(AMPK)是能量代谢动态平衡的重要调节因子，是多种代谢应激和衰老过程中的主要生存因子。代谢综合征与低度慢性炎症有关，主要发生在脂肪组织。在衰老过程中也存在低水平的炎症。有研究表明，AMPK信号转导通路可抑制核因子-κB(NF-κB)系统诱导的炎症反应。核因子-κB亚基不是AMPK的直接磷酸化靶点，但核因子-κB信号的抑制是由AMPK的几个下游靶点介导的，如SIRT1、PGC-1α、P53和Forkhead box O(FOXO)因子。AMPK信号似乎可以促进能量代谢，同时可以抑制与慢性应激有关的炎症反应，例如在营养过载和衰老过程中。AMPK可以抑制内质网和氧化应激，而内质网和氧化应激参与代谢紊乱和衰老过程。有趣的是，AMPK的许多靶蛋白都是所谓的长寿因子，如SIRT1、P53和FoxOS，它们不仅可以提高许多生物的抗逆性，延长生命周期，而且还可以抑制炎症反应。AMPK的活化能力在代谢应激和衰老过程中下降，可能加重代谢性疾病，加速衰老过程。我们将对参与抑制NF-κB信号转导和抑制炎症的AMPK通路进行综述。我们还强调，AMPK抑制炎症反应的能力可以对健康和寿命产生重大影响。
Adenosine monophosphate-activated protein kinase (AMPK) is a crucial regulator of energy metabolic homeostasis and thus a major survival factor in a variety of metabolic stresses and also in the aging process. Metabolic syndrome is associated with a low-grade, chronic inflammation, primarily in adipose tissue. A low-level of inflammation is also present in the aging process. There are emerging results indicating that AMPK signaling can inhibit the inflammatory responses induced by the nuclear factor-κB (NF-κB) system. The NF-κB subunits are not direct phosphorylation targets of AMPK, but the inhibition of NF-κB signaling is mediated by several downstream targets of AMPK, e.g., SIRT1, PGC-1α, p53, and Forkhead box O (FoxO) factors. AMPK signaling seems to enhance energy metabolism while it can repress inflammatory responses linked to chronic stress, e.g., in nutritional overload and during the aging process. AMPK can inhibit endoplasmic reticulum and oxidative stresses which are involved in metabolic disorders and the aging process. Interestingly, many target proteins of AMPK are so-called longevity factors, e.g., SIRT1, p53, and FoxOs, which not only can increase the stress resistance and extend the lifespan of many organisms but also inhibit the inflammatory responses. The activation capacity of AMPK declines in metabolic stress and with aging which could augment the metabolic diseases and accelerate the aging process. We will review the AMPK pathways involved in the inhibition of NF-κB signaling and suppression of inflammation. We also emphasize that the capacity of AMPK to repress inflammatory responses can have a significant impact on both healthspan and lifespan.
登录
查看更多内容
AMP激活的蛋白激酶对ULK1（HATG1）的磷酸化将能量传感连接到线粒体。
DOI：
10.1126/science.1196371
发表时间：
2011-01-28
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Egan DF;Shackelford DB;Mihaylova MM;Gelino S;Kohnz RA;Mair W;Vasquez DS;Joshi A;Gwinn DM;Taylor R;Asara JM;Fitzpatrick J;Dillin A;Viollet B;Kundu M;Hansen M;Shaw RJ
通讯作者：
Shaw RJ
影响因子：
2.8
作者：
Goodman, JE;Hofseth, LJ;Harris, CC
通讯作者：
Harris, CC
影响因子：
10.8
作者：
Alvarez-Guardia, David;Palomer, Xavier;Vazquez-Carrera, Manuel
通讯作者：
Vazquez-Carrera, Manuel
影响因子：
7.8
作者：
Curtis, R;O'Connor, G;DiStefano, PS
通讯作者：
DiStefano, PS
影响因子：
4.8
作者：
Ak, Prashanth;Levine, Arnold J.
通讯作者：
Levine, Arnold J.