A critical role of nicotinamide phosphoribosyltransferase in human telomerase reverse transcriptase induction by resveratrol in aortic smooth muscle cells.

Abstract	Aging is the predominant risk factor for cardiovascular diseases and contributes to a considerably more severe outcome in patients with acute myocardial infarction. Resveratrol, a polyphenol found in red wine, is a caloric restriction mimetic with potential anti-aging properties which has emerged as a beneficial nutraceutical for patients with cardiovascular disease. Although resveratrol is widely consumed as a nutritional supplement, its mechanism of action remains to be elucidated fully. Here, we report that resveratrol activates human nicotinamide phosphoribosyltransferase (NAMPT), SIRT4 and telomerase reverse transcriptase (hTERT) in human aortic smooth muscle cells. Similar observations were obtained in resveratrol treated C57BL/6J mouse heart and liver tissues. Resverotrol can also augment telomerase activity in both human pulmonary microvascular endothelial cells and A549 cells. Blocking NAMPT and SIRT4 expression prevents induction of hTERT in human aortic smooth muscle cells while overexpression of NAMPT elevates the telomerase activity induced by resveratrol in A549 cells. Together, these results identify a NAMPT-SIRT4-hTERT axis as a novel mechanism by which resveratrol may affect the anti-aging process in human aortic smooth muscle cells, mouse hearts and other cells. These findings enrich our understanding of the positive effects of resveratrol in human cardiovascular diseases.
Authors	Peixin Huang, Sean M Riordan, Daniel P Heruth, Dmitry N Grigoryev, Li Qin Zhang, Shui Qing Ye
Journal	Oncotarget (Oncotarget) Vol. 6 Issue 13 Pg. 10812-24 (May 10 2015) ISSN: 1949-2553 [Electronic] United States
PMID	25926556 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Cytokines Mitochondrial Proteins Stilbenes Nicotinamide Phosphoribosyltransferase nicotinamide phosphoribosyltransferase, human nicotinamide phosphoribosyltransferase, mouse TERT protein, human Telomerase Tert protein, mouse SIRT4 protein, human SIRT4 protein, mouse Sirtuins Resveratrol
Topics	Animals Aorta (drug effects, enzymology) Cell Line, Tumor Cellular Senescence (drug effects) Cytokines (genetics, metabolism) Dose-Response Relationship, Drug Enzyme Induction Female Humans Male Mice, Inbred C57BL Mitochondrial Proteins (metabolism) Muscle, Smooth, Vascular (drug effects, enzymology) Myocytes, Smooth Muscle (drug effects, enzymology) Nicotinamide Phosphoribosyltransferase (genetics, metabolism) RNA Interference Resveratrol Signal Transduction (drug effects) Sirtuins (metabolism) Stilbenes (pharmacology) Telomerase (biosynthesis, genetics, metabolism) Time Factors Transfection

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