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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Desquiret-dumas, Valérie Henrion, Daniel Nivet-antoine, Valérie Ayer, Audrey Vessières, Emilie Ferré, Marc Baron, Stéphanie Chupin, Stéphanie Bonneau, Dominique Procaccio, Vincent Reynier, Pascal Gueguen, Naïg Leman, Géraldine Chevrollier, Arnaud |
| Description | Author Affiliation: Desquiret-Dumas V ( From Angers Université, Angers F-49000, France.) |
| Abstract | Resveratrol (RSV) has been shown to be involved in the regulation of energetic metabolism, generating increasing interest in therapeutic use. SIRT1 has been described as the main target of RSV. However, recent reports have challenged the hypothesis of its direct activation by RSV, and the signaling pathways remain elusive. Here, the effects of RSV on mitochondrial metabolism are detailed both in vivo and in vitro using murine and cellular models and isolated enzymes. We demonstrate that low RSV doses (1-5 µM) directly stimulate NADH dehydrogenases and, more specifically, mitochondrial complex I activity (EC50 â ¼1 µM). In HepG2 cells, this complex I activation increases the mitochondrial NAD(+)/NADH ratio. This higher NAD(+) level initiates a SIRT3-dependent increase in the mitochondrial substrate supply pathways (i.e. the tricarboxylic acid cycle and fatty acid oxidation). This effect is also seen in liver mitochondria of RSV-fed animals (50 mg/kg/day). We conclude that the increase in NADH oxidation by complex I is a crucial event for SIRT3 activation by RSV. Our results open up new perspectives in the understanding of the RSV signaling pathway and highlight the critical importance of RSV doses used for future clinical trials. |
| ISSN | 00219258 |
| e-ISSN | 1083351X |
| Journal | Journal of Biological Chemistry |
| Issue Number | 51 |
| Volume Number | 288 |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology (United States) |
| Publisher Date | 2013-12-20 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Electron Transport Complex I Metabolism Hepatocytes Drug Effects NAD Sirtuin 3 Stilbenes Pharmacology Animals Enzyme Activation Hep G2 Cells Mice Mice, Inbred C57BL Mitochondria, Liver Oxidation-Reduction Research Support, Non-U.S. Gov't Biochemistry Molecular Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
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