Reference - Detail
|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|
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.
|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|
|Human and Animal Cells||PC-12(RCB0009)|