The ancient drug salicylate directly activates AMP-activated protein kinase
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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The ancient drug salicylate directly activates AMP-activated protein kinase. / Hawley, Simon A.; Fullerton, Morgan D.; Ross, Fiona A.; Schertzer, Jonathan D.; Chevtzoff, Cyrille; Walker, Katherine J.; Peggie, Mark W.; Zibrova, Darya; Green, Kevin A.; Mustard, Kirsty J.; Kemp, Bruce E.; Sakamoto, Kei; Steinberg, Gregory R.; Hardie, D. Grahame.
I: Science, Bind 336, Nr. 6083, 18.05.2012, s. 918-922.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - The ancient drug salicylate directly activates AMP-activated protein kinase
AU - Hawley, Simon A.
AU - Fullerton, Morgan D.
AU - Ross, Fiona A.
AU - Schertzer, Jonathan D.
AU - Chevtzoff, Cyrille
AU - Walker, Katherine J.
AU - Peggie, Mark W.
AU - Zibrova, Darya
AU - Green, Kevin A.
AU - Mustard, Kirsty J.
AU - Kemp, Bruce E.
AU - Sakamoto, Kei
AU - Steinberg, Gregory R.
AU - Hardie, D. Grahame
PY - 2012/5/18
Y1 - 2012/5/18
N2 - 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 More recently, it has been replaced by synthetic derivatives such as aspirin and salsalate, both of which are rapidly broken down to salicylate in vivo. At concentrations reached in plasma after administration of salsalate or of 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, threonine-172. In AMPK knockout mice, effects of salicylate to increase fat utilization and to 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.
AB - 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 More recently, it has been replaced by synthetic derivatives such as aspirin and salsalate, both of which are rapidly broken down to salicylate in vivo. At concentrations reached in plasma after administration of salsalate or of 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, threonine-172. In AMPK knockout mice, effects of salicylate to increase fat utilization and to 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.
UR - http://www.scopus.com/inward/record.url?scp=84861222690&partnerID=8YFLogxK
U2 - 10.1126/science.1215327
DO - 10.1126/science.1215327
M3 - Journal article
AN - SCOPUS:84861222690
VL - 336
SP - 918
EP - 922
JO - Science
JF - Science
SN - 0036-8075
IS - 6083
ER -
ID: 239567317