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- Title
Novel Role of HAX-1 in Neurons Protection After Spinal Cord Injury Involvement of IRE-1.
- Authors
Chen, Jiajia; Yang, Saishuai; Wu, Chunshuai; Cui, Zhiming; Wan, Yangyang; Xu, Guanhua; Bao, Guofeng; Zhang, Jinlong; Chen, Chu; Song, Dianwen
- Abstract
Spinal cord injury (SCI) is one of the diseases with high probability of causing disability in human beings, and there is no reliable treatment at present. Neuronal apoptosis is a vital component of secondary injury and plays a critical role in the development of neurological dysfunction after spinal cord injury. In this study, we found that the expression and distribution of HAX-1 in neurons increased 1 day after SCI. PC12 cells overexpressing HAX-1 showed decreased apoptosis and PC12 cells are more likely to undergo apoptosis after down-regulating HAX-1, which was confirmed via TUNEL experiments. We found GRP94 showed the same trend as HAX-1 in expression and interacted with HAX-1 and IRE-1 in both spinal cord tissue and PC12 cells, and this interaction seems to be enhanced after SCI. When the expression of HAX-1 was up-regulated, GRP94 also increased, but IRE-1 did not change at all. Further studies showed that overexpression of HAX-1 decreased the expression of pIRE-1, rather than IRE-1, and downstream proteins of the IRE signaling pathway (Caspase12, pJNK and CHOP) were significantly reduced, and vice versa. In animals treated with HAX-1 expressing adenovirus there are more neuronal cells remaining in the damaged spinal cord tissue, and hindlimb motor function of rats was significantly improved. So, we speculate that HAX-1 might play a role in protecting neurons from apoptosis after SCI by regulating the IRE-1 signaling pathway via promoting the dissociation of GRP94 from IRE-1. This may provide a theoretical basis and a potential therapeutic target for clinical improvement of neural function recovery after SCI.
- Subjects
SPINAL cord injuries; NEURONS; APOPTOSIS; SPINAL cord; CERVICAL cord; ADENOVIRUS diseases; HUMAN beings
- Publication
Neurochemical Research, 2020, Vol 45, Issue 10, p2302
- ISSN
0364-3190
- Publication type
Article
- DOI
10.1007/s11064-020-03088-x