SirT1--a sensor for monitoring self-renewal and aging process in retinal stem cells.
Retinal stem cells bear potency of proliferation, self-renewal, and differentiation into many retinal cells. Utilizing appropriate sensors one can effectively detect the self-renewal and aging process abilities. Silencing information regulator (SirT1), a member of the sirtuin family, is a NAD-dependent histone deacetylase and an essential mediator for longevity in normal cells by calorie restriction. We firstly investigate the SirT1 mRNA expression in retinal stem cells from rats and 19 human eyes of different ages. Results revealed that SirT1 expression was significantly decreased in in vivo aged eyes, associated with poor self-renewal abilities. Additionally, SirT1 mRNA levels were dose-dependently increased in resveratrol- treated retinal stem cells. The expression of SirT1 on oxidative stress-induced damage was significantly decreased, negatively correlated with the level of intracellular reactive oxygen species production. Treatment with resveratrol could effectively further reduce oxidative stress induced by H(2)O(2) treatment in retinal stem cells. Importantly, the anti-oxidant effects of resveratrol in H(2)O(2)-treated retinal stem cells were significantly abolished by knockdown of SirT1 expression (sh-SirT1). SirT1 expression provides a feasible sensor in assessing self-renewal and aging process in retinal stem cells. Resveratrol can prevent reactive oxygen species-induced damages via increased retinal SirT1 expression.
Department of Ophthalmology, Shin Kong Wu Ho-Su Memorial Hospital and Fu-Jen Catholic University, Taipei 11101, Taiwan. chpeng1008@gmail.com
Chi-Hsien
CH
Peng
Yuh-Lih
YL
Chang
Chung-Lan
CL
Kao
Ling-Ming
LM
Tseng
Chih-Chia
CC
Wu
Yu-Chih
YC
Chen
Ching-Yao
CY
Tsai
Lin-Chung
LC
Woung
Jorn-Hon
JH
Liu
Shih-Hwa
SH
Chiou
Shih-Jen
SJ
Chen
D000328:Adult; D000368:Aged; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D015374:Biosensing Techniques / Q000379:methods; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D002648:Child; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008991:Monitoring, Physiologic / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077185:Resveratrol; D012160:Retina / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D056564:Sirtuin 1 / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D013267:Stilbenes / Q000494:pharmacology; D055815:Young Adult
D000975:Antioxidants; D013267:Stilbenes; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D000077185:Resveratrol