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Involvement of p38 MAPK in the Drug Resistance of Refractory Epilepsy Through the Regulation Multidrug Resistance-Associated Protein 1.

Wang C, Hong Z, Chen Y - Neurochem. Res. (2015)

Bottom Line: However, the mechanism of up-regulated expression is still unclear.In our previous study, we have found that the MAPK signaling pathway mediated the expression of P-glycoprotein.The result showed that SB202190, the specific inhibitor of p38 MAPK, could down-regulate the expression of MRP1, while increase the concentrations of valproate and lamotrigine in hippocampus extracellular fluid of refractory epileptic rat.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Jinshan Hospital, Fudan University, 1508 Longhang Road, Shanghai, 201508, China.

ABSTRACT
Increased expression of multidrug-resistance associated protein 1 in brain tissue has been reported which lead to multidrug resistance of refractory epilepsy. However, the mechanism of up-regulated expression is still unclear. In our previous study, we have found that the MAPK signaling pathway mediated the expression of P-glycoprotein. So in this study, we used a rat model of refractory epilepsy to examine whether p38 MAPK affect the expression of MRP1 and the concentrations of AEDs in the brain. The expression of MRP1 and p38 MAPK was detected by immunofluorescence, Western-blot and real time-PCR, while the concentration of AEDs was measured by microdialysis and HPLC. The result showed that SB202190, the specific inhibitor of p38 MAPK, could down-regulate the expression of MRP1, while increase the concentrations of valproate and lamotrigine in hippocampus extracellular fluid of refractory epileptic rat. We demonstrate that p38 MAPK signaling pathway may be involved in drug resistance of refractory epilepsy by regulating MRP1.

No MeSH data available.


Related in: MedlinePlus

a MRP1 and p38 MAPK protein expression in the rat brain. b Quantitative analysis of western blot. **p < 0.01, *p < 0.05 compared with the control group; △p < 0.05 compared with the epilepsy group
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Fig2: a MRP1 and p38 MAPK protein expression in the rat brain. b Quantitative analysis of western blot. **p < 0.01, *p < 0.05 compared with the control group; △p < 0.05 compared with the epilepsy group

Mentions: Similarly, Western blot results showed that the expression of MRP1, p38 and p-p38 protein was significantly increased in the hippocampus and cortex in epilepsy group compared with the control group (p < 0.01). After SB202190 administration, the protein expression of MRP1, p38 and p-p38 decreased significantly compared with that in the epilepsy group (p < 0.05; Fig. 2a, b).Fig. 2


Involvement of p38 MAPK in the Drug Resistance of Refractory Epilepsy Through the Regulation Multidrug Resistance-Associated Protein 1.

Wang C, Hong Z, Chen Y - Neurochem. Res. (2015)

a MRP1 and p38 MAPK protein expression in the rat brain. b Quantitative analysis of western blot. **p < 0.01, *p < 0.05 compared with the control group; △p < 0.05 compared with the epilepsy group
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4493797&req=5

Fig2: a MRP1 and p38 MAPK protein expression in the rat brain. b Quantitative analysis of western blot. **p < 0.01, *p < 0.05 compared with the control group; △p < 0.05 compared with the epilepsy group
Mentions: Similarly, Western blot results showed that the expression of MRP1, p38 and p-p38 protein was significantly increased in the hippocampus and cortex in epilepsy group compared with the control group (p < 0.01). After SB202190 administration, the protein expression of MRP1, p38 and p-p38 decreased significantly compared with that in the epilepsy group (p < 0.05; Fig. 2a, b).Fig. 2

Bottom Line: However, the mechanism of up-regulated expression is still unclear.In our previous study, we have found that the MAPK signaling pathway mediated the expression of P-glycoprotein.The result showed that SB202190, the specific inhibitor of p38 MAPK, could down-regulate the expression of MRP1, while increase the concentrations of valproate and lamotrigine in hippocampus extracellular fluid of refractory epileptic rat.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Jinshan Hospital, Fudan University, 1508 Longhang Road, Shanghai, 201508, China.

ABSTRACT
Increased expression of multidrug-resistance associated protein 1 in brain tissue has been reported which lead to multidrug resistance of refractory epilepsy. However, the mechanism of up-regulated expression is still unclear. In our previous study, we have found that the MAPK signaling pathway mediated the expression of P-glycoprotein. So in this study, we used a rat model of refractory epilepsy to examine whether p38 MAPK affect the expression of MRP1 and the concentrations of AEDs in the brain. The expression of MRP1 and p38 MAPK was detected by immunofluorescence, Western-blot and real time-PCR, while the concentration of AEDs was measured by microdialysis and HPLC. The result showed that SB202190, the specific inhibitor of p38 MAPK, could down-regulate the expression of MRP1, while increase the concentrations of valproate and lamotrigine in hippocampus extracellular fluid of refractory epileptic rat. We demonstrate that p38 MAPK signaling pathway may be involved in drug resistance of refractory epilepsy by regulating MRP1.

No MeSH data available.


Related in: MedlinePlus