Neural Regeneration Research ›› 2017, Vol. 12 ›› Issue (5): 779-786.doi: 10.4103/1673-5374.206649

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Neuroprotective effects of Activin A on endoplasmic reticulum stress-mediated apoptotic and autophagic PC12 cell death

Long-xing Xue1, Hong-yu Liu1, Yang Cui1, Yue Dong1, Jiao-qi Wang1, Qiu-ye Ji2, Jin-ting He1, Min Yao1, Ying-ying Wang1, Yan-kun Shao1, Jing Mang1, Zhong-xin Xu1   

  1. 1 Department of Neurology, China-Japan Union Hospital, Jilin University, Changchun, Jilin Province, China; 2 Research Center, China-Japan Union Hospital, Jilin University, Changchun, Jilin Province, China
  • Received:2017-04-20 Online:2017-05-15 Published:2017-05-15
  • Contact: Jing Mang or Zhong-xin Xu, mangjing@jlu.edu.cn or xuzhongxin999@aliyun.com.
  • Supported by:

    This study was supported by the National Natural Science Foundation of China, No. 81671159, No. 81371298; a grant from the Development of Science and Technology of Jilin Province of China, No. 20160101099JC, No. 20160101073JC; a grant from the Youth Scientific Research of Health and Family Planning Commission in Jilin Province of China, No. 2014Q022; a grant from the Frontier Interdiscipline Program of Norman Bethune Health Science Center of Jilin University of China, No. 2013107028; a grant from the Young Scholars Program of Norman Bethune Health Science Center of Jilin University of China, No. 2013207052.

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Abstract:

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.

Key words: nerve regeneration, Activin A, endoplasmic reticulum stress, apoptosis, autophagy, c-Jun N-terminal kinase, p38, neural regeneration