| Autor: |
Shao, Yiye, Wang, Cuicui, Hong, Zhen, Chen, Yinghui |
| Předmět: |
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| Zdroj: |
Journal of Neurochemistry; Mar2016, Vol. 136 Issue 5, p1096-1105, 10p |
| Abstrakt: |
It is widely recognized that P-glycoprotein (P-gp) mediates drug resistance in refractory epilepsy. However, the molecular mechanism underlying the up-regulation of P-gp expression remains unclear. Our previous studies have demonstrated that p38 mitogen-activated protein kinase ( MAPK) regulates P-gp expression in cultured K562 cells. However, a lack of in vivo research leaves unanswered questions regarding whether p38 MAPK regulates P-gp expression or drug resistance in refractory epilepsy. This in vivo study examined the effects of p38 MAPK on the expression of P-gp and mdr1 in the rat brain and quantified antiepileptic drug ( AED) concentrations in the hippocampal extracellular fluid. In addition, the role of p38 MAPK in electrical and behavioral activity in a rat epilepsy model was studied. The results indicated that p38 MAPK inhibition by SB202190 reduced P-gp expression, while increasing AED concentration in the hippocampal extracellular fluid in refractory epileptic rats. SB202190 also reduced the resistance to AEDs in drug-resistant rats and significantly reduced the severity of seizure activity. These results suggest that p38 MAPK could participate in drug resistance in refractory epilepsy through the regulation of P-gp. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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