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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

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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.

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References

  1. Brandt C, Bethmann K, Gastens AM et al (2006) The multidrug transporter hypothesis of drug resistance in epilepsy: proof-of-principle in a rat model of temporal lobe epilepsy. Neurobiol Dis 24(1):202–211

    Article  CAS  PubMed  Google Scholar 

  2. Schinkel AH (1999) P-Glycoprotein, a gatekeeper in the blood-brain barrier. Adv Drug Deliv Rev 36(2–3):179–194

    Article  CAS  PubMed  Google Scholar 

  3. Sisodiya SM, Lin WR, Harding BN et al (2002) Drug resistance in epilepsy: expression of drug resistance proteins in common causes of refractory epilepsy. Brain 125(Pt 1):22–31

    Article  CAS  PubMed  Google Scholar 

  4. Marchi N, Hallene KL, Kight KM et al (2004) Significance of MDR1 and multiple drug resistance in refractory human epileptic brain. BMC Med 2:37

    Article  PubMed Central  PubMed  Google Scholar 

  5. Wu H, Hait WN, Yang JM (2003) Small interfering RNA-induced suppression of MDR1 (P-glycoprotein) restores sensitivity to multidrug-resistant cancer cells. Cancer Res 63(7):1515–1519

    CAS  PubMed  Google Scholar 

  6. Gottesman MM (2002) Mechanisms of cancer drug resistance. Annu Rev Med 53:615–627

    Article  CAS  PubMed  Google Scholar 

  7. Haar CP, Hebbar P, Wallace GCt et al (2012) Drug resistance in glioblastoma: a mini review. Neurochem Res 37(6):1192–1200

    Article  CAS  PubMed  Google Scholar 

  8. Ding Z, Yang L, Xie X et al (2010) Expression and significance of hypoxia-inducible factor-1 alpha and MDR1/P-glycoprotein in human colon carcinoma tissue and cells. J Cancer Res Clin Oncol 136(11):1697–1707

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. Wang GL, Jiang BH, Rue EA et al (1995) Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension. Proc Natl Acad Sci USA 92(12):5510–5514

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Comerford KM, Wallace TJ, Karhausen J et al (2002) Hypoxia-inducible factor-1-dependent regulation of the multidrug resistance (MDR1) gene. Cancer Res 62(12):3387–3394

    CAS  PubMed  Google Scholar 

  11. Williamson PD, French JA, Thadani VM et al (1993) Characteristics of medial temporal lobe epilepsy: II. Interictal and ictal scalp electroencephalography, neuropsychological testing, neuroimaging, surgical results, and pathology. Ann Neurol 34(6):781–787

    Article  CAS  PubMed  Google Scholar 

  12. Kwan P, Arzimanoglou A, Berg AT et al (2010) Definition of drug resistant epilepsy: consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies. Epilepsia 51(6):1069–1077

    Article  CAS  PubMed  Google Scholar 

  13. Wang Y, Zhou D, Wang B et al (2003) A kindling model of pharmacoresistant temporal lobe epilepsy in Sprague–Dawley rats induced by coriaria lactone and its possible mechanism. Epilepsia 44(4):475–488

    Article  PubMed  Google Scholar 

  14. Zhou H, Tang YH, Zheng Y (2006) A new rat model of acute seizures induced by tutin. Brain Res 1092(1):207–213

    Article  CAS  PubMed  Google Scholar 

  15. Racine RJ (1972) Modification of seizure activity by electrical stimulation. II. Motor seizure. Electroencephalogr Clin Neurophysiol 32(3):281–294

    Article  CAS  PubMed  Google Scholar 

  16. Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25(4):402–408

    Article  CAS  PubMed  Google Scholar 

  17. Feldmann M, Asselin M-C, Liu J, Wang S et al (2013) P-glycoprotein expression and function in patients with temporal lobe epilepsy: a case-control study. Lancet Neurol 12(8):777–785

    Article  CAS  PubMed  Google Scholar 

  18. Song X, Liu X, Chi W et al (2006) Hypoxia-induced resistance to cisplatin and doxorubicin in non-small cell lung cancer is inhibited by silencing of HIF-1alpha gene. Cancer Chemother Pharmacol 58(6):776–784

    Article  CAS  PubMed  Google Scholar 

  19. Huang LE, Gu J, Schau M et al (1998) Regulation of hypoxia-inducible factor 1alpha is mediated by an O2-dependent degradation domain via the ubiquitin–proteasome pathway. Proc Natl Acad Sci USA 95(14):7987–7992

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. Maglajlija V, Walker MC, Kovac S (2012) Severe ictal hypoxemia following focal, subclinical temporal electrographic scalp seizure activity. Epilepsy Behav 24(1):143–145

    Article  PubMed  Google Scholar 

  21. Blum AS, Ives JR, Goldberger AL et al (2000) Oxygen desaturations triggered by partial seizures: implications for cardiopulmonary instability in epilepsy. Epilepsia 41(5):536–541

    Article  CAS  PubMed  Google Scholar 

  22. Tae WS, Joo EY, Kim JH et al (2005) Cerebral perfusion changes in mesial temporal lobe epilepsy: SPM analysis of ictal and interictal SPECT. Neuroimage 24(1):101–110

    Article  PubMed  Google Scholar 

  23. Oommen KJ, Saba S, Oommen JA et al (2004) The relative localizing value of interictal and immediate postictal SPECT in seizures of temporal lobe origin. J Nucl Med 45(12):2021–2025

    PubMed  Google Scholar 

  24. Vielhaber S, Von Oertzen JH, Kudin AF et al (2003) Correlation of hippocampal glucose oxidation capacity and interictal FDG-PET in temporal lobe epilepsy. Epilepsia 44(2):193–199

    Article  CAS  PubMed  Google Scholar 

  25. Matheja P, Kuwert T, Ludemann P et al (2001) Temporal hypometabolism at the onset of cryptogenic temporal lobe epilepsy. Eur J Nucl Med 28(5):625–632

    Article  CAS  PubMed  Google Scholar 

  26. Eid T, Brines ML, Cerami A et al (2004) Increased expression of erythropoietin receptor on blood vessels in the human epileptogenic hippocampus with sclerosis. J Neuropathol Exp Neurol 63(1):73–83

    CAS  PubMed  Google Scholar 

  27. Rigau V, Morin M, Rousset MC et al (2007) Angiogenesis is associated with blood–brain barrier permeability in temporal lobe epilepsy. Brain 130(Pt 7):1942–1956

    Article  PubMed  Google Scholar 

  28. Chen W, Ostrowski RP, Obenaus A et al (2009) Prodeath or prosurvival: two facets of hypoxia inducible factor-1 in perinatal brain injury. Exp Neurol 216(1):7–15

    Article  CAS  PubMed Central  PubMed  Google Scholar 

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (no. 81371425), the scientific research foundation of Sichuan University for outstanding young scholars (no. 2082604164246), Sichuan Province basic research plan project (no. 2013JY0168) and Chengdu City Science and Technology Bureau fund (no. 12DXYB209JH-002).

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Authors and Affiliations

  1. Department of Neurology, West China Hospital, Sichuan University, No. 37 Wainan Guoxue Road, Chengdu, 610041, Sichuan, China

    Yaohua Li, Tianfang Zeng, Lei Chen & Dong Zhou

  2. Department of Neurosurgery, West China Hospital, Sichuan University, No. 37 Wainan Guoxue Road, Chengdu, 610041, Sichuan, China

    Jianbin Chen & Ding Lei

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  1. Yaohua Li
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  2. Jianbin Chen
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  3. Tianfang Zeng
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  4. Ding Lei
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  5. Lei Chen
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  6. Dong Zhou
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Correspondence to Lei Chen or Dong Zhou.

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Lei Chen and Dong Zhou, as the co-corresponding authors, contributed equally to this study.

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Li, Y., Chen, J., Zeng, T. et al. 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. Neurol Sci 35, 1203–1208 (2014). https://doi.org/10.1007/s10072-014-1681-0

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  • DOI: https://doi.org/10.1007/s10072-014-1681-0

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