Brain region-specific regulation of histone acetylation and efflux transporters in mice

Dahea You, Hye Min Shin, Fatimah Mosaad, Jason R. Richardson, Lauren M. Aleksunes

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Multidrug resistance protein 1 (MDR1) and breast cancer resistance protein (BCRP) protect the brain by restricting the passage of chemicals across the blood-brain barrier. Prior studies have demonstrated the epigenetic regulation of MDR1 and BCRP in cancer cells treated with histone deacetylase (HDAC) inhibitors that enhance histone acetylation and gene transcription. In the present study, we tested the in vivo effects of two HDAC inhibitors, valproic acid (VPA; 400 mg/kg) and apicidin (5 mg/kg), on Mdr1 and Bcrp transporter expression in brain regions of adult male mice injected intraperitoneally daily for 7 days. VPA increased Mdr1 protein expression in the striatum (70%) and Bcrp protein in the midbrain (30%). Apicidin enhanced striatal Mdr1 protein (30%) and hippocampal Bcrp protein (20%). Transporter induction correlated with increased histone H3 acetylation in discrete brain regions. In conclusion, HDAC inhibitors upregulate transporter proteins in vivo, which may be important in regulating regional xenobiotic disposition within the brain.

Original languageEnglish (US)
Article numbere22318
JournalJournal of Biochemical and Molecular Toxicology
Volume33
Issue number6
DOIs
StatePublished - Jun 1 2019

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Toxicology
  • Health, Toxicology and Mutagenesis

Keywords

  • Abcb1
  • Abcg2
  • P-glycoprotein
  • brain
  • breast cancer resistance protein (BCRP)
  • histone deacetylase (HDAC) inhibitor
  • multidrug resistance protein 1 (MDR1)
  • transporter

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