title: SIRT1 is required for the effects of rapamycin on high glucose-inducing mesangial cells senescence.
abstract: The mTOR deregulation has a role in chronic kidney disease including diabetic nephropathy. SIRT1 is an important participant in renal cytoprotective responses to aging and stress. However, whether both mTOR and SIRT1 are involved in high glucose-inducing mesangial cells (MCs) senescence still remains to be explored. Hence we investigate the potential functional interrelationship between these two proteins in high glucose-inducing MCs senescence. High glucose increased mTOR expression and activity, but decreased SIRT1 expression and activity. The level of mTOR was increased significantly, while the SIRT1 expression and activity was declined significantly with serial cell culture passage. The siRNA-SIRT1 and nicotinamide promoted MCs senescence. NAD or resveratrol arrested high glucose-inducing MCs senescence. Meanwhile, the effects of NAD or resveratrol on high glucose-inducing MCs senescence were also completely blocked by SiRNA-SIRT1. Rapamycin arrested MCs senescence induced by high glucose and prevented MCs senescence with serial cell culture passage, and meanwhile increased the SIRT1 expression and activity. Moreover, the effects of rapamycin on MCs senescence induced by high glucose were also completely blocked by treating cells with niacinamide or siRNA-SIRT1. These findings provide support for the hypothesis that SIRT1 is required for the effects of rapamycin on high glucose-inducing MCs senescence.
authors.affiliation: Department of Nephrology, State Key Laboratory of Kidney Diseases, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853, People's Republic of China.
authors.forename: Sifang
authors.initials: S
authors.lastname: Zhang
authors.forename: Guangyan
authors.initials: G
authors.lastname: Cai
authors.forename: Bo
authors.initials: B
authors.lastname: Fu
authors.forename: Zhe
authors.initials: Z
authors.lastname: Feng
authors.forename: Rui
authors.initials: R
authors.lastname: Ding
authors.forename: Xueyuan
authors.initials: X
authors.lastname: Bai
authors.forename: Weiping
authors.initials: W
authors.lastname: Liu
authors.forename: Li
authors.initials: L
authors.lastname: Zhuo
authors.forename: Lin
authors.initials: L
authors.lastname: Sun
authors.forename: Fuyou
authors.initials: F
authors.lastname: Liu
authors.forename: Xiangmei
authors.initials: X
authors.lastname: Chen
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D020868:Gene Silencing; D006943:Hyperglycemia / Q000378:metabolism*; D008297:Male; D050527:Mesangial Cells / Q000187:drug effects* / Q000378:metabolism; D009536:Niacinamide / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D000077185:Resveratrol; D020123:Sirolimus / Q000494:pharmacology*; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism*; D013267:Stilbenes / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D014803:Vitamin B Complex / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D013267:Stilbenes; D014803:Vitamin B Complex; D009536:Niacinamide; C546845:mTOR protein, rat; D058570:TOR Serine-Threonine Kinases; C488368:Sirt1 protein, rat; D056564:Sirtuin 1; D000077185:Resveratrol; D020123:Sirolimus