HMGB1 regulates P-glycoprotein expression in status epilepticus rat brains via the RAGE/NF-κB signaling pathway

Xie,Yuan; Yu,Nian; Chen,Yan; Zhang,Kang; Ma,Hai‑Yan; Di,Qing

doi:10.3892/mmr.2017.6772

HMGB1 regulates P-glycoprotein expression in status epilepticus rat brains via the RAGE/NF-κB signaling pathway

Authors:
- Yuan Xie
- Nian Yu
- Yan Chen
- Kang Zhang
- Hai‑Yan Ma
- Qing Di
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Affiliations: Department of Neurology, Nanjing Brain Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
Published online on: June 14, 2017 https://doi.org/10.3892/mmr.2017.6772
Pages: 1691-1700
Copyright: © Xie et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Overexpression of P-glycoprotein (P-gp) in the brain is an important mechanism involved in drug‑resistant epilepsy (DRE). High-mobility group box 1 (HMGB1), an inflammatory cytokine, significantly increases following seizures and may be involved in upregulation of P‑gp. However, the underlying mechanisms remain elusive. The aim of the present study was to evaluate the role of HMGB1 and its downstream signaling components, receptor for advanced glycation end‑product (RAGE) and nuclear factor‑κB (NF‑κB), on P‑gp expression in rat brains during status epilepticus (SE). Small interfering RNA (siRNA) was administered to rats prior to induction of SE by pilocarpine, to block transcription of the genes encoding HMGB1 and RAGE, respectively. An inhibitor of NF‑κB, pyrrolidinedithiocarbamic acid (PDTC), was utilized to inhibit activation of NF‑κB. The expression levels of HMGB1, RAGE, phosphorylated‑NF‑κB p65 (p‑p65) and P‑gp were detected by western blotting. The relative mRNA expression levels of the genes encoding these proteins were measured using reverse transcription‑quantitative polymerase chain reaction and the cellular localization of the proteins was determined by immunofluorescence. Pre‑treatment with HMGB1 siRNA reduced the expression levels of RAGE, p‑p65 and P‑gp. PDTC reduced the expression levels of P‑gp. These findings suggested that overexpression of P‑gp during seizures may be regulated by HMGB1 via the RAGE/NF‑κB signaling pathway, and may be a novel target for treating DRE.

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