1,25-(OH)2D3 protects pancreatic beta cells against H2O2-induced apoptosis through inhibiting the PERK-ATF4-CHOP pathway  

作　　者：Xiaobo Hu Cong Hu Jun Liu Zhuan Wu Tingting Duan Zhaohui Cao 

机构地区：[1]The Key Laboratory of Ecological Environment and Critical Human Diseases Prevention of Hunan Province Department of Education,Department of Biochemistry,Hengyang Medical School,University of South China,Hengyang 421001,China [2]Department of Biochemistry,Hengyang Medical School,University of South China,Hengyang 421001,China [3]The Key Laboratory of Typical Environmental Pollution and Health Hazards,University of South China,Hengyang 421001,China [4]Yiyang Central Hospital,Yiyang 413000,China

出　　处：《Acta Biochimica et Biophysica Sinica》2021年第1期46-53,共8页生物化学与生物物理学报（英文版）

基　　金：This work was supported by the grants from the Nature Science Fund of Hunan Province(Nos.14JJ3104 and 2016JJ2113);the Science Fund of Hunan Provincial Education Department(No.16A186);the Graduate Education and Innovation Fund of University of South China(Nos.2017JG022 and 2019JG029).

摘　　要：Endoplasmic reticulum(ER)stress plays a critical role in pancreaticβcell destruction which leads to the pathogenesis of type 1 diabetes mellitus(T1DM).Vitamin D(VD)has been reported to reduce the risk of T1DM;however,it remains unknown whether VD affects ER stress in pancreaticβcells.In this study,we investigated the role of the active form of VD,1,25-dihydroxyvitamin D3[1,25-(OH)2D3],in ER stress-inducedβcell apoptosis and explored its potential mechanism in mouse insulinoma cell line mouse insulinoma 6(MIN6).The results of cell counting kit-8(CCK8)and flow cytometric analyses showed that 1,25-(OH)2D3 caused a significant increase in the viability of MIN6 cells injured by H2O2.The protein kinase like ER kinase(PERK)signal pathway,one of the most conserved branches of ER stress,was found to be involved in this process.H2O2 activated the phosphorylation of PERK,upregulated the activating transcription factor 4(ATF4)and C/EBP homologous protein(CHOP)expression,and subsequently initiated cell apoptosis,which were significantly reversed by 1,25-(OH)2D3 pretreatment.In addition,GSK2606414,a specific inhibitor of PERK,suppressed PERK phosphorylation and reduced the expressions of ATF4 and CHOP,leading to a significant decrease inβcell apoptosis induced by H2O2.Taken together,the present findings firstly demonstrated that 1,25-(OH)2D3 could prevent MIN6 cells against ER stress-associated apoptosis by inhibiting the PERK-ATF4-CHOP pathway.Therefore,our results suggested that 1,25-(OH)2D3 might serve as a potential therapeutic target for preventing pancreaticβcell destruction in T1DM.

关 键 词：MIN6 cells endoplasmic reticulum stress PERK 1 25-(OH)2D3 diabetes 

分 类 号：R576[医药卫生—消化系统]