Salidroside protects cortical neurons against glutamate-induced cytotoxicity by inhibiting autophagy

Recent evidence suggests that glutamate-induced cytotoxicity contributes to autophagic neuron death and is partially mediated by increased oxidative stress. Salidroside has been demonstrated to have neuroprotective effects in glutamate-induced neuronal damage. The precise mechanism of its regulatory...

Full description

Saved in:
Bibliographic Details
Published in:Molecular and cellular biochemistry 2016-08, Vol.419 (1-2), p.53-64
Main Authors: Yin, Wei-Yong, Ye, Qiang, Huang, Huan-Jie, Xia, Nian-Ge, Chen, Yan-Yan, Zhang, Yi, Qu, Qiu-Min
Format: Article
Language:English
Subjects:
Amino acids
Analysis
Animals
Apoptosis
Autophagy
Autophagy - drug effects
Biochemistry
Biomedical and Life Sciences
Cardiology
Cell Survival - drug effects
Cerebral Cortex - metabolism
Cerebral Cortex - pathology
Cytotoxicity
Glucosides - pharmacology
Glutamate
Glutamic Acid - toxicity
Life Sciences
Medical Biochemistry
Nerve Tissue Proteins - metabolism
Neurons
Neurons - metabolism
Neurons - pathology
Oncology
Phenols - pharmacology
Phytochemicals
Rats
Rats, Sprague-Dawley
RNA
Signal Transduction - drug effects
Tumor proteins
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Recent evidence suggests that glutamate-induced cytotoxicity contributes to autophagic neuron death and is partially mediated by increased oxidative stress. Salidroside has been demonstrated to have neuroprotective effects in glutamate-induced neuronal damage. The precise mechanism of its regulatory role in neuronal autophagy is, however, poorly understood. This study aimed to probe the effects and mechanisms of salidroside in glutamate-induced autophagy activation in cultured rat cortical neurons. Cell viability assay, Western blotting, coimmunoprecipitation, and small interfering RNA were performed to analyze autophagy activities during glutamate-evoked oxidative injury. We found that salidroside protected neonatal neurons from glutamate-induced apoptotic cell death. Salidroside significantly attenuated the LC3-II/LC3-I ratio and expression of Beclin-1, but increased (SQSTM1)/p62 expression under glutamate exposure. Pretreatment with 3-methyladenine (3-MA), an autophagy inhibitor, decreased LC3-II/LC3-I ratio, attenuated glutamate-induced cell injury, and mimicked some of the protective effects of salidroside against glutamate-induced cell injury. Molecular analysis demonstrated that salidroside inhibited cortical neuron autophagy in response to glutamate exposure through p53 signaling by increasing the accumulation of cytoplasmic p53. Salidroside inhibited the glutamate-induced dissociation of the Bcl-2-Beclin-1 complex with minor affects on the PI3K/Akt/mTOR signaling pathways. These data demonstrate that the inhibition of autophagy could be responsible for the neuroprotective effects of salidroside on glutamate-induced neuronal injury.
ISSN:0300-8177
1573-4919
DOI:10.1007/s11010-016-2749-3