CIIA 通过阻断 ASK1 介导的信号转导来防止 SOD1(G93A)诱导的细胞毒性。
CIIA prevents SOD1(G93A)-induced cytotoxicity by blocking ASK1-mediated signaling.
机构信息
Laboratory of Cell Death and Human Diseases, Department of Life Sciences, School of Life Sciences and Biotechnology, Korea University Seoul, South Korea.
Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University Seoul, South Korea.
出版信息
Front Cell Neurosci. 2014 Jun 26;8:179. doi: 10.3389/fncel.2014.00179. eCollection 2014.
Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease with higher selectivity in degeneration of motor neurons. However, the molecular mechanism by which the ALS-linked mutants of human superoxide dismutase 1 (SOD1) gene induce neurotoxicity remains obscure yet. Here, we show that depletion of CIIA expression by RNA interference (RNAi) promoted cytotoxicity caused by ALS-linked G93A mutant of the SOD1 gene. The RNAi-mediated knockdown of CIIA also enhanced the SOD1(G93A)-induced interaction between ASK1 and TRAF2 as well as ASK1 activity. Furthermore, endogenous silencing of CIIA by RNAi augmented the effects of SOD1(G93A) on reduction of mitochondria membrane potential (Δψm), release of cytochrome c into the cytoplasm, and caspase activation. Together, our results suggest that CIIA negatively modulates ASK1-mediated cytotoxic signaling processes in a SOD1(G93A)-expressing cellular model of ALS.
肌萎缩侧索硬化症（ALS）是一种成人发病的神经退行性疾病，其运动神经元的退化具有更高的选择性。然而，导致 ALS 相关人类超氧化物歧化酶 1（SOD1）基因突变体诱导神经毒性的分子机制尚不清楚。在这里，我们发现 RNA 干扰（RNAi）下调 CIIA 的表达促进了由 ALS 相关的 SOD1 基因 G93A 突变体引起的细胞毒性。RNAi 介导的 CIIA 敲低还增强了 SOD1(G93A)诱导的 ASK1 和 TRAF2 之间的相互作用以及 ASK1 的活性。此外，CIIA 的内源性 RNAi 沉默增强了 SOD1(G93A)对线粒体膜电位（Δψm）降低、细胞色素 c 向细胞质释放和半胱天冬酶激活的影响。综上所述，我们的研究结果表明，CIIA 负调控 ALS 表达细胞模型中 ASK1 介导的细胞毒性信号通路。
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