1. Neuroprotective effects of Activin A on endoplasmic reticulum stress-mediated apoptotic and autophagic PC12 cell death
- Author
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Yang Cui, Qiu-Ye Ji, Long-Xing Xue, Jiaoqi Wang, Hongyu Liu, Yue Dong, Jing Mang, Yingying Wang, Jinting He, Zhongxin Xu, Min Yao, and Yankun Shao
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Programmed cell death ,autophagy ,Thapsigargin ,p38 mitogen-activated protein kinases ,p38 ,Biology ,lcsh:RC346-429 ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Developmental Neuroscience ,Internal medicine ,nerve regeneration ,Activin A ,endoplasmic reticulum stress ,apoptosis ,c-Jun N-terminal kinase ,neural regeneration ,medicine ,ASK1 ,lcsh:Neurology. Diseases of the nervous system ,Endoplasmic reticulum ,Autophagy ,Cell biology ,030104 developmental biology ,Endocrinology ,chemistry ,Apoptosis ,Tumor necrosis factor alpha ,030217 neurology & neurosurgery ,Research Article - 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.
- Published
- 2017