The molecular regulatory mechanism of co-treatment with LA and PCA on P38 MAPK signaling pathway in the neurons of TX suckling mice
10.3969/j.issn.1002-0152.2017.08.009
- VernacularTitle:α-硫辛酸联合青霉胺对TX乳鼠神经元P38MAPK通路的调控作用研究
- Author:
Chenchen XU
1
;
Jianjian DONG
;
Nan CHENG
;
Xun WANG
;
Xuen YU
Author Information
1. 安徽中医药大学神经病学研究所附属医院神经内科 合肥230061
- Keywords:
Apoptosis;
Wilson's disease;
Oxidative stress;
Neurotoxicity
- From:
Chinese Journal of Nervous and Mental Diseases
2017;43(8):490-495
- CountryChina
- Language:Chinese
-
Abstract:
Objective To detect the molecular regulatory mechanism of co-treatment with LA and PCA on P38 MAPK signaling Pathway in the Neurons of Wilson's Disease Model-TX mice.Methods The neurons of TX suckling mice were isolated and cultured by primary method,and were divided into control group,model group,ALA group,PCA group and combined group.Flow cytometry was used to analyze the expression of ROS and JC-1.Western blot was used to detect the expression of P38 MAPK,Cyt C,Caspase 9 and Caspase 3.Results Flow cytometry results showed that MFI of ROS was 59.29±1.22,53.19±1.34 and 52.46±1.23 in ALA,PCA and co-treatment.ALA,PCA and co-treatment could significantly reduce the release of ROS and enhance the fluorescence intensity of JC-1 (P＜0.01).Compared with ALA group and PCA group,combined group could reduce the release of ROS and significantly enhance the fluorescence intensity of JC-1.Western blot indicated that the expression levels of P38 MAPK,Cyt C,Caspase 9,Caspase 3 in the neurons of model group had a remarkable increase compared with control group.Compared with the model group,the three treatment groups could decrease the expression levels of P38 MAPK,Cyt C,Caspase 9 and Caspase 3 in the neurons of TX suckling mice (P＜0.01).Meanwhile,the protein levels of P38 MAPK,Cyt C,Caspase 9 and Caspase 3 had a significant decrease compared with ALA group and PCA group.Conclusion he present findings suggest that co-treatment with LA and PCA can increase the copper excretion,reduce copper-induced mitochondria damage and attenuate the neurotoxicity,which in turn decrease neuronal apoptosis and improve neurological impairment of WD.
