A Nampt inhibitor FK866 mimics vitamin B3 deficiency by causing senescence of human fibroblastic Hs68 cells via attenuation of NAD(+)-SIRT1 signaling

Biogerontology
Tuzz-Ying SongNae-Cherng Yang

Abstract

Vitamin B3 (niacin) deficiency can cause pellagra with symptoms of dermatitis, diarrhea and dementia. However, it is unclear whether the vitamin B3 deficiency causes human aging. FK866 (a Nampt inhibitor) can reduce intracellular NAD(+) level and induce senescence of human Hs68 cells. However, the mechanisms underlying FK866-induced senescence of Hs68 cells are unclear. In this study, we used FK866 to mimic the effects of vitamin B3 deficiency to reduce the NAD(+) level and investigated the mechanisms of FK866-induced senescence of Hs68 cells. We hypothesized that FK866 induced the senescence of Hs68 cells via an attenuation of NAD(+)-silent information regulator T1 (SIRT1) signaling. We found that FK866 induced cell senescence and diminished cellular NAD(+) levels and SIRT1 activity (detected by acetylation of p53), and these effects were dramatically antagonized by co-treatment with nicotinic acid, nicotinamide, or NAD(+). In contrast, the protein expression of SIRT1, AMP-activated protein kinase, mammalian target of rapamycin, and nicotinamide phosphoribosyltransferase (Nampt) was not affected by FK866. In addition, the role of GSH in the FK866-induced cells senescence may be limited, as N-acetylcysteine did not antagonize F...Continue Reading

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Citations

Nov 28, 2017·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Fiqri D KhaidizarYasumasa Bessho
Dec 6, 2018·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Giovanna SocialiSantina Bruzzone
Jun 4, 2016·Molecular Medicine·Zhiqiang ZhaoLijun Di
Feb 15, 2017·Frontiers in Physiology·Chiara de LuciaSandrine Thuret
Jun 16, 2021·Journal of Photochemistry and Photobiology. B, Biology·Takeshi KatayoshiKentaro Tsuji-Naito

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