The ancient drug salicylate directly activates AMP-activated protein kinase.
The ancient drug salicylate directly activates AMP-activated protein kinase.
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DOI：
10.1126/science.1215327
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发表时间：
2012-05-18
期刊：
影响因子：
--
通讯作者：
Hardie DG
中科院分区：
文献类型：
--
作者：
Hawley SA;Fullerton MD;Ross FA;Schertzer JD;Chevtzoff C;Walker KJ;Peggie MW;Zibrova D;Green KA;Mustard KJ;Kemp BE;Sakamoto K;Steinberg GR;Hardie DG
水杨酸盐是一种植物产物，自古以来就有药用价值。最近，它已被合成衍生物取代，如阿司匹林和双水杨酸酯，两者在体内迅速分解为水杨酸酯。在施用双水杨酯或高剂量阿司匹林后血浆中达到的浓度下，水杨酸盐激活腺苷一磷酸活化蛋白激酶（AMPK），这是细胞生长和代谢的中心调节剂。水杨酸盐与合成激活剂A-769662结合在同一位点，引起变构激活并抑制活化磷酸化位点Thr 172的去磷酸化。在AMPK基因敲除小鼠中，水杨酸盐在体内增加脂肪利用和降低血浆脂肪酸的作用丧失。我们的研究结果表明，AMPK激活可以解释双水杨酯和阿司匹林在人类中的一些有益作用。
Salicylate, a plant product, has been in medicinal use since ancient times. More recently it has been replaced by synthetic derivatives such as aspirin and salsalate, both rapidly broken down to salicylate in vivo. At concentrations reached in plasma following administration of salsalate, or aspirin at high doses, salicylate activates adenosine monophosphate-activated protein kinase (AMPK), a central regulator of cell growth and metabolism. Salicylate binds at the same site as the synthetic activator, A-769662, to cause allosteric activation and inhibition of dephosphorylation of the activating phosphorylation site, Thr172. In AMPK knockout mice, effects of salicylate to increase fat utilization and lower plasma fatty acids in vivo were lost. Our results suggest that AMPK activation could explain some beneficial effects of salsalate and aspirin in humans.
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DOI：
10.1073/pnas.1009705107
发表时间：
2010-11-09
影响因子：
11.1
作者：
Oakhill, Jonathan S.;Chen, Zhi-Ping;Kemp, Bruce E.
通讯作者：
Kemp, Bruce E.
影响因子：
3.5
作者：
Davies, SP;Helps, NR;Hardie, DG
通讯作者：
Hardie, DG
影响因子：
39.2
作者：
Goldfine AB;Fonseca V;Jablonski KA;Pyle L;Staten MA;Shoelson SE;TINSAL-T2D (Targeting Inflammation Using Salsalate in Type 2 Diabetes) Study Team
通讯作者：
TINSAL-T2D (Targeting Inflammation Using Salsalate in Type 2 Diabetes) Study Team
影响因子：
64.8
作者：
Xiao, Bing;Sanders, Matthew J.;Underwood, Elizabeth;Heath, Richard;Mayer, Faith V.;Carmena, David;Jing, Chun;Walker, Philip A.;Eccleston, John F.;Haire, Lesley F.;Saiu, Peter;Howell, Steven A.;Aasland, Rein;Martin, Stephen R.;Carling, David;Gamblin, Steven J.
通讯作者：
Gamblin, Steven J.
影响因子：
15.9
作者：
Hundal, RS;Petersen, KF;Shulman, GI
通讯作者：
Shulman, GI