title: Expression of HIF-1α and MDR1/P-glycoprotein in refractory mesial temporal lobe epilepsy patients and pharmacoresistant temporal lobe epilepsy rat model kindled by coriaria lactone.
abstract: Hypoxia-inducible factor-1α (HIF-1α) is thought to mediate pharmacoresistance in tumor by inducing Pgp overexpression. We aimed to investigate the expression of HIF-1α and MDR1/P-glycoprotein in refractory epilepsy, to explore the correlation of HIF-1α with epilepsy multidrug resistance. We collected hippocampus and mesial temporal lobe (MTL) cortex of refractory mesial temporal lobe epilepsy (mTLE) patients that underwent surgery, and established a pharmacoresistant TLE rat model kindled by coriaria lactone. We used real-time quantitative PCR (RQ-PCR) and western blot to investigate expression of HIF-1α and MDR1 in hippocampus and MTL/entorhinal cortex. We found that the expression of HIF-1α and MDR1, at both mRNA and protein levels, were up-regulated in hippocampus and MTL cortex of mTLE patients compared with the control cortex (all P < 0.05), and increased in hippocampus and entorhinal cortex of kindled rat model versus the control group (all P < 0.05). These results demonstrated the overexpression of HIF-1α and MDR1/Pgp in hippocampus and MTL/entorhinal cortex of mTLE patients and the pharmacoresistant TLE rat model. HIF-1α may have a regulatory effect on MDR1 expression in refractory epilepsy, which is probably consistent with MDR mechanism in tumor.
authors.affiliation: Department of Neurology, West China Hospital, Sichuan University, No. 37 Wainan Guoxue Road, Chengdu, 610041, Sichuan, China.
authors.forename: Yaohua
authors.initials: Y
authors.lastname: Li
authors.forename: Jianbin
authors.initials: J
authors.lastname: Chen
authors.forename: Tianfang
authors.initials: T
authors.lastname: Zeng
authors.forename: Ding
authors.initials: D
authors.lastname: Lei
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.forename: Dong
authors.initials: D
authors.lastname: Zhou
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000096:biosynthesis / Q000235:genetics; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis*; D000328:Adult; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology* / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000378:metabolism; D016022:Case-Control Studies; D002543:Cerebral Hemorrhage / Q000378:metabolism; D003292:Convulsants / Q000633:toxicity; D004195:Disease Models, Animal; D018432:Drug Resistance, Multiple / Q000235:genetics*; D018728:Entorhinal Cortex / Q000378:metabolism; D004833:Epilepsy, Temporal Lobe / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D005260:Female; D019450:Genes, MDR; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis* / Q000235:genetics; D007696:Kindling, Neurologic / Q000235:genetics*; D007783:Lactones / Q000633:toxicity; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation; D055815:Young Adult
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000927:Anticonvulsants; D003292:Convulsants; C497442:HIF1A protein, human; C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007783:Lactones; D009419:Nerve Tissue Proteins; C049836:coriaria lactone