1. Exogenous basic fibroblast growth factor inhibits ER stress-induced apoptosis and improves recovery from spinal cord injury.
- Author
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Zhang HY, Zhang X, Wang ZG, Shi HX, Wu FZ, Lin BB, Xu XL, Wang XJ, Fu XB, Li ZY, Shen CJ, Li XK, and Xiao J
- Subjects
- Animals, Caspase 12 metabolism, Disease Models, Animal, Female, GAP-43 Protein metabolism, Heat-Shock Proteins metabolism, In Situ Nick-End Labeling, Locomotion drug effects, Neurons metabolism, PC12 Cells, Phosphatidylinositol 3-Kinases, Proto-Oncogene Proteins c-akt, Rats, Rats, Sprague-Dawley, Severity of Illness Index, Signal Transduction drug effects, Time Factors, Transcription Factor CHOP metabolism, Up-Regulation drug effects, Apoptosis drug effects, Endoplasmic Reticulum Stress drug effects, Fibroblast Growth Factor 2 therapeutic use, Neurons drug effects, Recovery of Function drug effects, Spinal Cord Injuries drug therapy, Spinal Cord Injuries pathology, Spinal Cord Injuries physiopathology
- Abstract
Aim: To investigate the mechanism of endoplasmic reticulum (ER) stress-induced apoptosis as well as the protective action of basic fibroblast growth factor (bFGF) both in vivo and in vitro., Methods and Results: ER stress-induced apoptosis was involved in the injuries of spinal cord injury (SCI) model rat. bFGF administration improved the recovery and increased the survival of neurons in spinal cord lesions in model rat. The protective effect of bFGF is related to the inhibition of CHOP, GRP78 and caspase-12, which are ER stress-induced apoptosis response proteins. bFGF administration also increased the survival of neurons and the expression of growth-associated protein 43 (GAP43), which is related to neural regeneration. The protective effect of bFGF is related to the activation of downstream signals, PI3K/Akt/GSK-3β and ERK1/2, especially in the ER stress cell model., Conclusions: This is the first study to illustrate that the role of bFGF in SCI recovery is related to the inhibition of ER stress-induced cell death via the activation of downstream signals. Our work also suggested a new trend for bFGF drug development in central neural system injuries, which are involved in chronic ER stress-induced apoptosis., (© 2012 Blackwell Publishing Ltd.)
- Published
- 2013
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