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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

Concentration of LTG in the hippocampal extracellular fluid
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Fig5: Concentration of LTG in the hippocampal extracellular fluid

Mentions: Similarly, LTG was detected in the hippocampal extracellular fluid 30 min after administration in each group. In the control group, the highest concentrations of LTG in the hippocampal extracellular fluid was 73.87 ± 2.98 ng/ml at 60 min post-injection (Fig. 5). Both the epilepsy and the SB202190 group, LTG reached a peak at 90 min and gradually decreased thereafter. The LTG level found in the hippocampal extracellular fluid in the epilepsy group was much lower than those in the control group at each time point over 30–150 min (p = 0.000, 0.000, 0.002, 0.000 and 0.006, respectively). Moreover, SB202190 administration significantly increased LTG concentrations in the hippocampal extracellular fluid at each time point in the SB202190 group (p = 0.007, 0.006, 0.007, 0.010 and 0.046 vs. epilepsy group, respectively). The result indicated that the administration of SB202190 did not change the trend of fluctuation of LTG, but significantly increased the concentrations of LTG in the hippocampal extracellular fluid of epileptic rats.Fig. 5


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)

Concentration of LTG in the hippocampal extracellular fluid
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4493797&req=5

Fig5: Concentration of LTG in the hippocampal extracellular fluid
Mentions: Similarly, LTG was detected in the hippocampal extracellular fluid 30 min after administration in each group. In the control group, the highest concentrations of LTG in the hippocampal extracellular fluid was 73.87 ± 2.98 ng/ml at 60 min post-injection (Fig. 5). Both the epilepsy and the SB202190 group, LTG reached a peak at 90 min and gradually decreased thereafter. The LTG level found in the hippocampal extracellular fluid in the epilepsy group was much lower than those in the control group at each time point over 30–150 min (p = 0.000, 0.000, 0.002, 0.000 and 0.006, respectively). Moreover, SB202190 administration significantly increased LTG concentrations in the hippocampal extracellular fluid at each time point in the SB202190 group (p = 0.007, 0.006, 0.007, 0.010 and 0.046 vs. epilepsy group, respectively). The result indicated that the administration of SB202190 did not change the trend of fluctuation of LTG, but significantly increased the concentrations of LTG in the hippocampal extracellular fluid of epileptic rats.Fig. 5

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