Osthole ameliorates glutamate-induced toxicity in HT22 cells via activating PI3K/Akt signaling pathway.
10.11817/j.issn.1672-7347.2015.09.002
- Author:
Xiaoyuan MAO
1
;
Zhibin WANG
1
;
Honghao ZHOU
1
;
Zhaoqian LIU
1
;
Yong ZHOU
2
Author Information
1. Institute of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008; Institute of Clinical Pharmacology; Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha 410078, China.
2. Department of Orthopeadics, Third Xiangya Hospital, Central South University, Changsha 410013, China.
- Publication Type:Journal Article
- MeSH:
Animals;
Caspase 3;
metabolism;
Cell Line;
Cell Survival;
Chromones;
pharmacology;
Coumarins;
pharmacology;
Glutamic Acid;
adverse effects;
Hippocampus;
cytology;
Mice;
Morpholines;
pharmacology;
Neuroprotective Agents;
pharmacology;
Phosphatidylinositol 3-Kinases;
metabolism;
Phosphorylation;
Proto-Oncogene Proteins c-akt;
metabolism;
Signal Transduction
- From:
Journal of Central South University(Medical Sciences)
2015;40(9):955-959
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To investigate the neuroprotective effects of osthole (OST) on glutamate-induced toxicity in hippocampal HT22 cells and to explore the correlation between the protection and phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt) signaling pathway.
METHODS:The cell injury model of HT22 was induced by glutamate and the cell viability was detected by MTS assay. The lactate dehydrogenase (LDH) release and the caspase-3 activity were determined by commercial kits. Western blot analysis was utilized to detect the protein levels of PI3K, Akt, p-PI3K and p-Akt.
RESULTS:OST markedly improved the cell survival and decreased the LDH release in glutamate-treated HT22 cells in a dose-dependent manner. Furthermore, the levels of p-PI3K and p-Akt proteins were significantly increased in glutamate and OST-co-treated HT22 cells. The effect of OST on p-Akt phosphorylation in HT22 cells was attenuated in the presence of PI3K specific inhibitor (LY294002).
CONCLUSION:OST protects HT22 cells from glutamate excitotoxicity through a mechanism involving the activation of PI3K/Akt signaling pathway.