Estrogen reduces endoplasmic reticulum stress to protect against glucotoxicity induced-pancreatic 尾-cell death

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• 作者：Suwattanee Kooptiwut ; Pitchnischa Mahawong ; Wanthanee Hanchang ; Namoiy Semprasert ; Suchada Kaewin ; Thawornchai Limjindaporn ; Pa-thai Yenchitsomanus
• 关键词：ER ; endoplasmic reticulum ; UPR ; unfolded protein response ; GRP-78 ; glucose-regulated protein 78 ; CHOP ; CCAAT/enhancer-binding protein homologous protein ; PI ; propidium iodide ; MTT ; 3-(4 ; 5-dimethylthiazol-2-yl)-2 ; 5-diphenyl tetrazolium bromide thiazolyl blue ; ELISA ; enzyme-linked immunosorbent assay ; HRP ; horseradish peroxidase ; cDNA ; complementary DNA ; RIPA ; radioimmunoprecipitation assay ; BCA ; bicinchoninic acid ; SDS&ndash ; PAGE ; sodium dodecyl sulfate&ndash ; polyacrylamide gel electrophoresis ; E
• 刊名：The Journal of Steroid Biochemistry and Molecular Biology
• 出版年：January, 2014
• 年：2014
• 卷：139
• 期：Complete
• 页码：25-32
• 全文大小：1528 K

文摘

Estrogen can improve glucose homeostasis not only in diabetic rodents but also in humans. However, the molecular mechanism by which estrogen prevents pancreatic 尾-cell death remains unclear. To investigate this issue, INS-1 cells, a rat insulinoma cell line, were cultured in medium with either 11.1 mM or 40 mM glucose in the presence or the absence of estrogen. Estrogen significantly reduced apoptotic 尾-cell death by decreasing nitrogen-induced oxidative stress and the expression of the ER stress markers GRP 78, ATF6, P-PERK, PERK, uXBP1, sXBP1, and CHOP in INS-1 cells after prolonged culture in medium with 40 mM glucose. In contrast, estrogen increased the expression of survival proteins, including sarco/endoplasmic reticulum Ca²⁺ ATPase (SERCA-2), Bcl-2, and P-p38, in INS-1 cells after prolonged culture in medium with 40 mM glucose. The cytoprotective effect of estrogen was attenuated by addition of the estrogen receptor (ER伪 and ER尾) antagonist ICI 182,780 and the estrogen membrane receptor inhibitor G15. We showed that estrogen decreases not only oxidative stress but also ER stress to protect against 40 mM glucose-induced pancreatic 尾-cell death.