A critical role of nicotinamide phosphoribosyltransferase in human telomerase reverse transcriptase induction by resveratrol in aortic smooth muscle cells.
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.
Division of Experimental and Translational Genetics, Department of Pediatrics, Children's Mercy Hospitals and Clinics, University of Missouri Kansas City School of Medicine, Kansas City, MO, USA.
Peixin
P
Huang
Division of Experimental and Translational Genetics, Department of Pediatrics, Children's Mercy Hospitals and Clinics, University of Missouri Kansas City School of Medicine, Kansas City, MO, USA.
Sean M
SM
Riordan
Division of Experimental and Translational Genetics, Department of Pediatrics, Children's Mercy Hospitals and Clinics, University of Missouri Kansas City School of Medicine, Kansas City, MO, USA.
Daniel P
DP
Heruth
Division of Experimental and Translational Genetics, Department of Pediatrics, Children's Mercy Hospitals and Clinics, University of Missouri Kansas City School of Medicine, Kansas City, MO, USA.|Department of Biomedical and Health Informatics, University of Missouri Kansas City School of Medicine, Kansas City, MO, USA.|Laboratory of Translational Studies and Personalized Medicine, "Northern" BioPharm Cluster at Moscow Institute of Physics and Technology, Moscow Region, Russian Federation.
Dmitry N
DN
Grigoryev
Division of Experimental and Translational Genetics, Department of Pediatrics, Children's Mercy Hospitals and Clinics, University of Missouri Kansas City School of Medicine, Kansas City, MO, USA.
Li Qin
LQ
Zhang
Division of Experimental and Translational Genetics, Department of Pediatrics, Children's Mercy Hospitals and Clinics, University of Missouri Kansas City School of Medicine, Kansas City, MO, USA.|Department of Biomedical and Health Informatics, University of Missouri Kansas City School of Medicine, Kansas City, MO, USA.
Shui Qing
SQ
Ye
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000201:enzymology; D045744:Cell Line, Tumor; D016922:Cellular Senescence / Q000187:drug effects; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction; D005260:Female; D006801:Humans; D008297:Male; D008810:Mice, Inbred C57BL; D024101:Mitochondrial Proteins / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000201:enzymology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000201:enzymology; D054409:Nicotinamide Phosphoribosyltransferase / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects; D037761:Sirtuins / Q000378:metabolism; D013267:Stilbenes / Q000494:pharmacology*; D019098:Telomerase / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014162:Transfection
D016207:Cytokines; D024101:Mitochondrial Proteins; D013267:Stilbenes; D054409:Nicotinamide Phosphoribosyltransferase; C085455:nicotinamide phosphoribosyltransferase, human; C495867:nicotinamide phosphoribosyltransferase, mouse; C509186:TERT protein, human; D019098:Telomerase; C509187:Tert protein, mouse; C525357:SIRT4 protein, human; C514813:SIRT4 protein, mouse; D037761:Sirtuins; D000077185:Resveratrol
NAMPT; SIRT; aging; gerotarget; resveratrol; telomerase