Xue Long-Xing, Liu Hong-Yu, Cui Yang, Dong Yue, Wang Jiao-Qi, Ji Qiu-Ye, He Jin-Ting, Yao Min, Wang Ying-Ying, Shao Yan-Kun, Mang Jing, Xu Zhong-Xin
Department of Neurology, China-Japan Union Hospital, Jilin University, Changchun, Jilin Province, China.
Research Center, China-Japan Union Hospital, Jilin University, Changchun, Jilin Province, China.
Neural Regen Res. 2017 May;12(5):779-786. doi: 10.4103/1673-5374.206649.
Activin A, a member of the transforming growth factor-beta superfamily, plays a neuroprotective role in multiple neurological diseases. Endoplasmic reticulum (ER) stress-mediated apoptotic and autophagic cell death is implicated in a wide range of diseases, including cerebral ischemia and neurodegenerative diseases. Thapsigargin was used to induce PC12 cell death, and Activin A was used for intervention. Our results showed that Activin A significantly inhibited morphological changes in thapsigargin-induced apoptotic cells, and the expression of apoptosis-associated proteins [cleaved-caspase-12, C/EBP homologous protein (CHOP) and cleaved-caspase-3] and biomarkers of autophagy (Beclin-1 and light chain 3), and downregulated the expression of thapsigargin-induced ER stress-associated proteins [inositol requiring enzyme-1 (IRE1), tumor necrosis factor receptor-associated factor 2 (TRAF2), apoptosis signal-regulating kinase 1 (ASK1), c-Jun N-terminal kinase (JNK) and p38]. The inhibition of thapsigargin-induced cell death was concentration-dependent. These findings suggest that administration of Activin A protects PC12 cells against ER stress-mediated apoptotic and autophagic cell death by inhibiting the activation of the IRE1-TRAF2-ASK1-JNK/p38 cascade.
激活素A是转化生长因子-β超家族的成员之一，在多种神经系统疾病中发挥神经保护作用。内质网（ER）应激介导的凋亡和自噬性细胞死亡与多种疾病有关，包括脑缺血和神经退行性疾病。使用毒胡萝卜素诱导PC12细胞死亡，并使用激活素A进行干预。我们的结果表明，激活素A显著抑制了毒胡萝卜素诱导的凋亡细胞的形态变化，以及凋亡相关蛋白[裂解的半胱天冬酶-12、C/EBP同源蛋白（CHOP）和裂解的半胱天冬酶-3]和自噬生物标志物（Beclin-1和轻链3）的表达，并下调了毒胡萝卜素诱导的ER应激相关蛋白[肌醇需要酶-1（IRE1）、肿瘤坏死因子受体相关因子2（TRAF2）、凋亡信号调节激酶1（ASK1）、c-Jun氨基末端激酶（JNK）和p38]的表达。激活素A对毒胡萝卜素诱导的细胞死亡的抑制作用呈浓度依赖性。这些发现表明，给予激活素A可通过抑制IRE1-TRAF2-ASK1-JNK/p38级联反应的激活来保护PC12细胞免受ER应激介导的凋亡和自噬性细胞死亡。
