Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Maryland School of Medicine, Baltimore, MD.
Am J Obstet Gynecol. 2013 Oct;209(4):345.e1-7. doi: 10.1016/j.ajog.2013.06.037. Epub 2013 Jun 20.
Both oxidative stress and endoplasmic reticulum stress (ER stress) are causal events in diabetic embryopathy. We tested whether oxidative stress causes ER stress.
Wild-type (WT) and superoxide dismutase 1 (SOD1)-overexpressing day 8.75 embryos from nondiabetic WT control with SOD1 transgenic male and diabetic WT female with SOD1 transgenic male were analyzed for ER stress markers: C/EBP-homologous protein (CHOP), calnexin, eukaryotic initiation factor 2α (eIF2α), protein kinase ribonucleic acid (RNA)-like ER kinase (PERK), binding immunoglobulin protein, protein disulfide isomerase family A member 3, kinases inositol-requiring protein-1α (IRE1α), and the X-box binding protein (XBP1) messenger RNA (mRNA) splicing.
Maternal diabetes significantly increased the levels of CHOP, calnexin, phosphorylated (p)-eIF2α, p-PERK, and p-IRE1α; triggered XBP1 mRNA splicing; and enhanced ER chaperone gene expression in WT embryos. SOD1 overexpression blocked these diabetes-induced ER stress markers.
Mitigating oxidative stress via SOD1 overexpression blocks maternal diabetes-induced ER stress in vivo.
氧化应激和内质网应激（ER 应激）都是糖尿病胚胎病的因果事件。我们检测了氧化应激是否会引起 ER 应激。
分析了来自非糖尿病 WT 对照组的 WT 和超氧化物歧化酶 1（SOD1）过表达的第 8.75 天胚胎，这些胚胎的雄性携带有 SOD1 转基因，雌性为 WT 糖尿病患者且携带有 SOD1 转基因，以研究 ER 应激标志物：C/EBP 同源蛋白（CHOP）、钙连蛋白、真核起始因子 2α（eIF2α）、蛋白激酶 RNA 样内质网激酶（PERK）、结合免疫球蛋白蛋白、蛋白二硫键异构酶家族 A 成员 3、肌醇需求蛋白激酶 1α（IRE1α）和 X 盒结合蛋白（XBP1）信使 RNA（mRNA）剪接。
母体糖尿病显著增加了 WT 胚胎中 CHOP、钙连蛋白、磷酸化（p）-eIF2α、p-PERK 和 p-IRE1α 的水平；引发 XBP1 mRNA 剪接；并增强了 ER 伴侣基因的表达。SOD1 过表达阻断了这些由糖尿病引起的 ER 应激标志物。
通过 SOD1 过表达减轻氧化应激可阻断母体糖尿病引起的体内 ER 应激。
