School of Basic Medical Sciences, Department of Pathology, Ningxia Medical University; Ningxia Key Laboratory of Cerebrocranial Diseases, Yinchuan, Ningxia, P. R. China.
Department of Pharmaceutical Sciences, Biomanufacturing Research Institute and Technological Enterprise (BRITE), North Carolina Central University, Durham, North Carolina, USA.
Int J Biol Sci. 2017 Nov 1;13(11):1458-1469. doi: 10.7150/ijbs.21300. eCollection 2017.
Selenium and selenoproteins play important roles in neuroprotection against glutamate‑induced cell damage, in which mitochondrial dysfunction is considered a major pathogenic feature. Recent studies have revealed that mitochondrial fission could activates mitochondrial initiated cell death pathway. The objectives of the study are to determine whether glutamate induced cell death is mediated through mitochondrial initiated cell death pathway and activation of autophagy, and whether overexpression of selenoprotein H can protect cells from glutamate toxicity by preserving mitochondrial morphology and suppressing autophagy. Vector- or human selenoprotein H (SelH)-transfected HT22 cells (V-HT22 and SelH-HT22, respectively) were exposed to glutamate. The results showed that glutamate-induced cytotoxicity was associated with increased ROS production and imbalance in mitochondrial dynamics and autophagy. These alterations were reversed and cellular integrity restored by overexpression of SelH in HT22 cells.
硒和硒蛋白在神经保护对抗谷氨酸诱导的细胞损伤中发挥重要作用，其中线粒体功能障碍被认为是主要的发病特征。最近的研究表明，线粒体分裂可以激活线粒体引发的细胞死亡途径。本研究的目的是确定谷氨酸诱导的细胞死亡是否通过线粒体引发的细胞死亡途径和自噬的激活来介导，以及过表达硒蛋白 H 是否可以通过维持线粒体形态和抑制自噬来保护细胞免受谷氨酸毒性。将载体或人硒蛋白 H（SelH）转染的 HT22 细胞（分别为 V-HT22 和 SelH-HT22）暴露于谷氨酸中。结果表明，谷氨酸诱导的细胞毒性与 ROS 产生增加以及线粒体动力学和自噬失衡有关。这些改变通过在 HT22 细胞中过表达 SelH 得到逆转，恢复了细胞完整性。
