RRC ID 56096
Author Sun Z, Liu Y, Kong X, Wang R, Xu Y, Shang C, Huo J, Huang M, Zhao F, Bian K, Zhang S, Tu Y, Chen X.
Title Exendin-4 Plays a Protective Role in a Rat Model of Spinal Cord Injury Through SERCA2.
Journal Cell Physiol Biochem
Abstract BACKGROUND/AIMS:Current therapies for spinal cord injury (SCI) have limited efficacy, and identifying a therapeutic target is a pressing need. Sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 2 (SERCA2) plays an important role in regulating calcium homeostasis, which has been shown to inhibit apoptosis. Exendin-4 has been shown to inhibit the apoptosis of nerve cells in SCI, which can also improve SERCA2 expression. In this study, we sought to determine whether exendin-4 plays a protective role in a rat model of SCI via SERCA2.
METHODS:To investigate the effects of exendin-4 on SCI, a rat model of SCI was induced by a modified version of Allen's method. Spinal cord tissue sections from rats and western blot analysis were used to examine SERCA2 expression after treatment with the long-acting glucagon-like peptide 1 receptor exendin-4 or the SERCA2 antagonist 5(6)-carboxyfluorescein diacetate N-succinimidyl ester (CE). Locomotor function was evaluated using the Basso Beattie Bresnahan locomotor rating scale and slanting board test.
RESULTS:Cell apoptosis was increased with CE treatment and decreased with exendin-4 treatment. Upregulation of SERCA2 in female rats with SCI resulted in an improvement of motor function scores and histological changes.
CONCLUSION:These findings suggest that exendin-4 plays a protective role in a rat model of SCI through SERCA2 via inhibition of apoptosis. Existing drugs targeting SERCA2 may be an effective therapeutic strategy for the treatment of SCI.
Volume 47(2)
Pages 617-629
Published 2018-5-22
DOI 10.1159/000490017
PII 000490017
PMID 29794460
MeSH Animals Apoptosis / drug effects Caspase 3 / metabolism Cyclic AMP / metabolism Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors Cyclic AMP-Dependent Protein Kinases / metabolism Disease Models, Animal Exenatide Locomotion / drug effects Microscopy, Fluorescence PC12 Cells Peptides / pharmacology* Peptides / therapeutic use Protective Agents / pharmacology* Protective Agents / therapeutic use Proto-Oncogene Proteins c-bcl-2 / metabolism Rats Rats, Sprague-Dawley Recovery of Function / drug effects* Sarcoplasmic Reticulum Calcium-Transporting ATPases / antagonists & inhibitors Sarcoplasmic Reticulum Calcium-Transporting ATPases / metabolism* Signal Transduction / drug effects Spinal Cord Injuries / prevention & control Venoms / pharmacology* Venoms / therapeutic use bcl-2-Associated X Protein / metabolism
IF 5.5
Times Cited 2
Human and Animal Cells PC-12(RCB0009)