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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 expression in the rat brain (fluorescence microscope 400×). a Cortex of the control group; b Cortex of the epilepsy group; c Cortex of the SB202190 group; d Hippocampus CA1 region of the control group; e Hippocampus CA1 region of the epilepsy group; f Hippocampus CA1 region of the SB202190 group. b Quantitative analysis of immunofluorescence. MRP1-positive and p38 MAPK-positive cells were counted and at least 3 slices from each brain were measured. **p < 0.01 compared with the control group; △p < 0.05 compared with the epilepsy group
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Fig1: a MRP1 and p38 MAPK expression in the rat brain (fluorescence microscope 400×). a Cortex of the control group; b Cortex of the epilepsy group; c Cortex of the SB202190 group; d Hippocampus CA1 region of the control group; e Hippocampus CA1 region of the epilepsy group; f Hippocampus CA1 region of the SB202190 group. b Quantitative analysis of immunofluorescence. MRP1-positive and p38 MAPK-positive cells were counted and at least 3 slices from each brain were measured. **p < 0.01 compared with the control group; △p < 0.05 compared with the epilepsy group

Mentions: Immunofluorescence staining showed that the expression of MRP1 could be observed in the hippocampus and cerebral cortex of rats in each group. The Immunofluorescence images labeled with p38 MAPK (red) exhibiting cytoplasmic location in the control group and nuclear location in the epilepsy and SB202190 groups, while the membrane location for MRP1 (green) and the nuclear location for Dapi (blue) were observed in each group. The MRP1 and p38 MAPK-positive cells were significantly higher in both cortex and hippocampus CA1 region in epilepsy group than those in control group (p < 0.01). Compared with the epilepsy group, the number of MRP1 and p38 MAPK-positive cells were significantly decreased in SB202190 group (p < 0.05; Fig. 1a, b).Fig. 1


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 expression in the rat brain (fluorescence microscope 400×). a Cortex of the control group; b Cortex of the epilepsy group; c Cortex of the SB202190 group; d Hippocampus CA1 region of the control group; e Hippocampus CA1 region of the epilepsy group; f Hippocampus CA1 region of the SB202190 group. b Quantitative analysis of immunofluorescence. MRP1-positive and p38 MAPK-positive cells were counted and at least 3 slices from each brain were measured. **p < 0.01 compared with the control group; △p < 0.05 compared with the epilepsy group
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig1: a MRP1 and p38 MAPK expression in the rat brain (fluorescence microscope 400×). a Cortex of the control group; b Cortex of the epilepsy group; c Cortex of the SB202190 group; d Hippocampus CA1 region of the control group; e Hippocampus CA1 region of the epilepsy group; f Hippocampus CA1 region of the SB202190 group. b Quantitative analysis of immunofluorescence. MRP1-positive and p38 MAPK-positive cells were counted and at least 3 slices from each brain were measured. **p < 0.01 compared with the control group; △p < 0.05 compared with the epilepsy group
Mentions: Immunofluorescence staining showed that the expression of MRP1 could be observed in the hippocampus and cerebral cortex of rats in each group. The Immunofluorescence images labeled with p38 MAPK (red) exhibiting cytoplasmic location in the control group and nuclear location in the epilepsy and SB202190 groups, while the membrane location for MRP1 (green) and the nuclear location for Dapi (blue) were observed in each group. The MRP1 and p38 MAPK-positive cells were significantly higher in both cortex and hippocampus CA1 region in epilepsy group than those in control group (p < 0.01). Compared with the epilepsy group, the number of MRP1 and p38 MAPK-positive cells were significantly decreased in SB202190 group (p < 0.05; Fig. 1a, b).Fig. 1

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