title: SirT1 and STAT3 protect retinal pigmented epithelium cells against oxidative stress.
abstract: It has been previously demonstrated that there are interactions between sirtuin 1 (SirT1) and signal transducer and activator of transcription 3 (STAT3), which have versatile roles in various microenvironments. However, whether or not there is crosstalk between these two molecules during oxidative stress, and what mechanism of crosstalk occurs in retinal pigmented epithelium cells (RPEs), the protection of which may delay the process of age-related macular degeneration (AMD), has required further elucidation. The present study aimed to investigate the interactions between SirT1 and STAT3 in RPEs, following exposure to oxidative stress. The rates of proliferation and apoptosis, levels of intracellular reactive oxygen species and cell senescence of RPEs, induced by oxidants [H2O2 and oxidized low density lipoprotein (oxLDL)], were evaluated. The results revealed a downregulation of SirT1 expression, and an upregulation of STAT3 expression during oxidative stress. Further investigation indicated that SirT1 protected RPEs from oxidative stress-induced damage. Furthermore, gain- and loss-of-function experiments indicated that SirT1 had negative effects on the regulation of STAT3 expression in RPEs during oxidative stress. Notably, STAT3 directly protected the cells from oxidative stress, rather than depending on SirT1. Additionally, the protective effects of STAT3 had no association with the modulation of cell senescence during oxidative stress. In conclusion, SirT1 had negative effects on the regulation of STAT3 expression during oxidative stress. However, SirT1 and STAT3 demonstrated protective roles against oxidative stress in RPEs. These results therefore suggested that there was an equilibrium mechanism between SirT1 and STAT3 against oxidative stress, meaning that an equilibrium mechanism is required to be considered when combined application of STAT3 and SirT1 were performed to treat AMD.
authors.affiliation: Department of Ophthalmology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Langen
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Ophthalmology, Inner Mongolia People's Hospital, Hohhot, Inner Mongolia 010017, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.affiliation: Department of Ophthalmology, Inner Mongolia People's Hospital, Hohhot, Inner Mongolia 010017, P.R. China.
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Ophthalmology, Inner Mongolia People's Hospital, Hohhot, Inner Mongolia 010017, P.R. China.
authors.forename: Gerile
authors.initials: G
authors.lastname: Tu
authors.affiliation: Department of Neurology, Inner Mongolia People's Hospital, Hohhot, Inner Mongolia 010017, P.R. China.
authors.forename: Yanmei
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Neurology, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia 010017, P.R. China.
authors.forename: Jia
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Ophthalmology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Yiqiao
authors.initials: Y
authors.lastname: Xing
mesh_terms: D000975:Antioxidants; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D016922:Cellular Senescence; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009536:Niacinamide / Q000494:pharmacology; D018384:Oxidative Stress / Q000235:genetics*; D000077185:Resveratrol; D055213:Retinal Pigment Epithelium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D056564:Sirtuin 1 / Q000235:genetics* / Q000378:metabolism; D013267:Stilbenes / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D008077:Lipoproteins, LDL; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D013267:Stilbenes; C099252:oxidized low density lipoprotein; D009536:Niacinamide; D006861:Hydrogen Peroxide; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D000077185:Resveratrol