Resveratrol Ameliorates Aging-Related Metabolic Phenotypes by Inhibiting cAMP Phosphodiesterases
作者: Sung-Jun ParkFaiyaz AhmadAndrew PhilpKeith BaarTishan WilliamsHaibin LuoHengming KeHolger RehmannRonald TaussigAlexandra L. BrownMyung K. KimMichael A. BeavenAlex B. BurginVincent ManganielloJay H. Chung
作者单位: 1Laboratory of Obesity and Aging Research, Genetics and Developmental Biology Center, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
2Cardiovascular Pulmonary Branch, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
3Laboratory of Molecular Immunology, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
4Functional Molecular Biology Laboratory, University of California Davis, Davis, CA 95616, USA
5Department of Biochemistry and Biophysics, The University of North Carolina, Chapel Hill, NC 27599-7260, USA
6Structural Biology Lab, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, P. R. China
7Department of Molecular Cancer Research, Centre for Biomedical Genetics and Cancer Genomics Centre, University Medical Center, 3584 CG Utrecht, The Netherlands
8Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
9Emerald BioStructures, 7869 NE Day Road West, Bainbridge Island, WA 98110, USA
刊名: Cell, 2012, Vol.148 (3), pp.421-433
来源数据库: Elsevier Journal
DOI: 10.1016/j.cell.2012.01.017
原始语种摘要: Summary(#br)Resveratrol, a polyphenol in red wine, has been reported as a calorie restriction mimetic with potential antiaging and antidiabetogenic properties. It is widely consumed as a nutritional supplement, but its mechanism of action remains a mystery. Here, we report that the metabolic effects of resveratrol result from competitive inhibition of cAMP-degrading phosphodiesterases, leading to elevated cAMP levels. The resulting activation of Epac1, a cAMP effector protein, increases intracellular Ca 2+ levels and activates the CamKKβ-AMPK pathway via phospholipase C and the ryanodine receptor Ca 2+ -release channel. As a consequence, resveratrol increases NAD + and the activity of Sirt1. Inhibiting PDE4 with rolipram reproduces all of the metabolic benefits of resveratrol, including...
全文获取路径: Elsevier  (合作)
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影响因子:31.957 (2012)

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