Over‐expression of Nicotinamide phosphoribosyltransferase in mouse cells confers protective effect against oxidative and ER stress‐induced premature senescence

Nuriliani, Ardaning and Nakahata, Yasukazu and Ahmed, Rezwana and Khaidizar, Fiqri Dizar and Matsui, Takaaki and Bessho, Yasumasa (2020) Over‐expression of Nicotinamide phosphoribosyltransferase in mouse cells confers protective effect against oxidative and ER stress‐induced premature senescence. Genes to Cells, 25 (8). pp. 593-602. ISSN 1356-9597, DOI https://doi.org/10.1111/gtc.12794.

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Official URL: https://doi.org/10.1111/gtc.12794

Abstract

A main feature of aged organisms is the accumulation of senescent cells. Accumulated senescent cells, especially stress-induced premature senescent cells, in aged organisms lead to the decline of the regenerative potential and function of tissues. We recently reported that the over-expression of NAMPT, which is the rate-limiting enzyme in mammalian NAD+ salvage pathway, delays replicative senescence in vitro. However, whether Nampt-overexpressing cells are tolerant of stress-induced premature senescence remains unknown. Here, we show that primary mouse embryonic fibroblasts derived from Nampt-overexpressing transgenic mice (Nampt Tg-MEF cells) possess resistance against stress-induced premature senescence in vitro. We found that higher oxidative or endoplasmic reticulum (ER) stress is required to induce premature senescence in Nampt Tg-MEF cells compared to wild-type cells. Moreover, we found that Nampt Tg-MEF cells show acute expression of unfolded protein response (UPR)-related genes, which in turn would have helped to restore proteostasis and avoid cellular senescence. Our results demonstrate that NAMPT/NAD+ axis functions to protect cells not only from replicative senescence, but also from stress-induced premature senescence in vitro. We anticipate that in vivo activation of NAMPT activity or increment of NAD+ would protect tissues from the accumulation of premature senescent cells, thereby maintaining healthy aging. © 2020 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd

Item Type: Article
Funders: JSPS KAKENHI Grant Number 17K08569, Takeda Science Foundation, Directorate of Higher Education, The Ministry of Education and Culture of Indonesia, grant year 2014 (BPPLN-DIKTI, 2014)
Uncontrolled Keywords: ER stress; NAD+; NAMPT; oxidative stress; premature senescence
Subjects: Q Science > Q Science (General)
Q Science > QH Natural history
Divisions: Deputy Vice Chancellor (Research & Innovation) Office > Centre for Research in Biotechnology for Agriculture
Depositing User: Ms. Juhaida Abd Rahim
Date Deposited: 07 Sep 2020 01:51
Last Modified: 07 Sep 2020 01:51
URI: http://eprints.um.edu.my/id/eprint/25510

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