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Regulation of autophagy and ubiquitinated protein accumulation by bFGF promotes functional recovery and neural protection in a rat model of spinal cord injury.
- Source :
-
Molecular neurobiology [Mol Neurobiol] 2013 Dec; Vol. 48 (3), pp. 452-64. Date of Electronic Publication: 2013 Mar 21. - Publication Year :
- 2013
-
Abstract
- The role of autophagy in the recovery of spinal cord injury remains controversial; in particular, the mechanism of autophagy regulated degradation of ubiquitinated proteins has not been discussed to date. In this study, we investigated the protective role of basic fibroblast growth factor (bFGF) both in vivo and in vitro and demonstrated that excessive autophagy and ubiquitinated protein accumulation is involved in the rat model of trauma. bFGF administration improved recovery and increased the survival of neurons in spinal cord lesions in the rat model. The protective effect of bFGF is related to the inhibition of autophagic protein LC3II levels; bFGF treatment also enhances clearance of ubiquitinated proteins by p62, which also increases the survival of neuronal PC-12 cells. The activation of the downstream signals of the PI3K/Akt/mTOR pathway by bFGF treatment was detected both in vivo and in vitro. Combination therapy including the autophagy activator rapamycin partially abolished the protective effect of bFGF. The present study illustrates that the role of bFGF in SCI recovery is related to the inhibition of excessive autophagy and enhancement of ubiquitinated protein clearance via the activation of PI3K/Akt/mTOR signaling. Overall, our study suggests a new trend for bFGF drug development for central nervous system injuries and sheds light on protein signaling involved in bFGF action.
- Subjects :
- Animals
Disease Models, Animal
Female
Fibroblast Growth Factor 2 administration & dosage
Fibroblast Growth Factor 2 pharmacology
Heat-Shock Proteins metabolism
Humans
Motor Neurons drug effects
Motor Neurons metabolism
Motor Neurons pathology
Neuroprotective Agents pharmacology
PC12 Cells
Phosphatidylinositol 3-Kinases metabolism
Proto-Oncogene Proteins c-akt metabolism
Rats
Rats, Sprague-Dawley
Sequestosome-1 Protein
Signal Transduction drug effects
Sirolimus pharmacology
Spinal Cord Injuries drug therapy
Spinal Cord Injuries enzymology
TOR Serine-Threonine Kinases metabolism
Autophagy drug effects
Fibroblast Growth Factor 2 therapeutic use
Neuroprotective Agents therapeutic use
Recovery of Function drug effects
Spinal Cord Injuries pathology
Spinal Cord Injuries physiopathology
Ubiquitinated Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1559-1182
- Volume :
- 48
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Molecular neurobiology
- Publication Type :
- Academic Journal
- Accession number :
- 23516099
- Full Text :
- https://doi.org/10.1007/s12035-013-8432-8