Finding a Target for Resveratrol
| Autor: | Eriko Michishita-Kioi, Ruth I. Tennen, Katrin F. Chua |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
endocrine system diseases
Biochemistry Genetics and Molecular Biology(all) organic chemicals food and beverages AMPK Phosphodiesterase Computational biology Resveratrol Pharmacology Health benefits Biology Article General Biochemistry Genetics and Molecular Biology chemistry.chemical_compound chemistry Mechanism of action Molecular targets medicine medicine.symptom skin and connective tissue diseases hormones hormone substitutes and hormone antagonists |
| Zdroj: | Cell. 148:387-389 |
| ISSN: | 0092-8674 |
| DOI: | 10.1016/j.cell.2012.01.032 |
| Popis: | 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 Ca2+ levels and activates the CamKKβ-AMPK pathway via phospholipase C and the ryanodine receptor Ca2+-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 prevention of diet-induced obesity and an increase in mitochondrial function, physical stamina, and glucose tolerance in mice. Therefore, administration of PDE4 inhibitors may also protect against and ameliorate the symptoms of metabolic diseases associated with aging. |
| Databáze: | OpenAIRE |
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