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18/05/2012

Intérêt de l'aspirine

Une explication sur l'intérêt de prendre de l'aspirine tous les jours.

lu sur :

http://www.sciencemag.org/content/vol336/issue6083/twis.dtl

This Week in SCIENCE
18 May 2012, 336 (6083) 

An Aspirin a Day? 

The protein kinase AMPK (adenosine monophosphate-activated protein kinase) directly monitors cellular energy stores as reflected by changes in cellular concentrations of AMP, adenosine diphosphate (ADP), and adenosine triphosphate (ATP). Through phosphorylation of its targets, it helps to control metabolism, polarity, autophagy, and the restraint of cell proliferation. Activation of AMPK is also proposed to be beneficial for the treatment of diseases, including cancer and diabetes. Hawley et al. (p. 918, published online 19 April; see the Perspective by Shaw and Cantley) (report that AMPK can be activated by high concentrations of salicylate, a compound derived from the very commonly used drug aspirin. In mice, salicylate promoted fatty acid and carbohydrate metabolism in an AMPK-dependent fashion.

Science 18 May 2012: 
Vol. 336 no. 6083 pp. 813-814 
DOI: 10.1126/science.1223140
  • PERSPECTIVE

CELL BIOLOGY

Ancient Sensor for Ancient Drug

  1. Reuben J. Shaw1
  2. Lewis C. Cantley2

+Author Affiliations

  1. 1Howard Hughes Medical Institute, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
  2. 2Beth Israel Deaconess Medical Center, Boston, MA 02115, USA.
  1. E-mail: shaw@salk.edulewis_cantley@hms.harvard.edu

Salicylate, a compound found in willow tree bark, is the active breakdown product of aspirin, and has been used for medicinal purposes since ancient times. However, the molecular mechanism underlying the beneficial effects of salicylate has been unclear. On page 918 of this issue, Hawley et al. (1) show that salicylate activates the cellular metabolic regulator adenosine monophosphate (AMP)–activated protein kinase (AMPK), which stimulates fat utilization in mice.

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Science 18 May 2012: 
Vol. 336 no. 6083 pp. 918-922 
DOI: 10.1126/science.1215327

  • REPORT

The Ancient Drug Salicylate Directly Activates AMP-Activated Protein Kinase

  1. Simon A. Hawley1
  2. Morgan D. Fullerton2
  3. Fiona A. Ross1
  4. Jonathan D. Schertzer2
  5. Cyrille Chevtzoff1,
  6. Katherine J. Walker1
  7. Mark W. Peggie3
  8. Darya Zibrova3
  9. Kevin A. Green1
  10. Kirsty J. Mustard1,
  11. Bruce E. Kemp4
  12. Kei Sakamoto3,*
  13. Gregory R. Steinberg2,4
  14. D. Grahame Hardie1,

+Author Affiliations

  1. 1Division of Cell Signalling and Immunology, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UK.
  2. 2Divisions of Endocrinology and Metabolism, Department of Medicine, and Department of Biochemistry and Biomedical Sciences, McMaster University, 1200 Main Street West, Hamilton, Ontario L8N 3Z5, Canada.
  3. 3Medical Research Council Protein Phosphorylation Unit, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UK.
  4. 4St. Vincent’s Institute of Medical Research and Department of Medicine, University of Melbourne, 41 Victoria Parade, Fitzroy, Vic 3065 Australia.

+Author Notes

  • * Present address: Nestlé Institute of Health Sciences Société Anonyme, Campus École Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.

  1. To whom correspondence should be addressed: E-mail: d.g.hardie@dundee.ac.uk

ABSTRACT

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.

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