Brain region-specific regulation of histone acetylation and efflux transporters in mice.
ATP Binding Cassette Transporter, Subfamily B, Member 1
/ biosynthesis
ATP Binding Cassette Transporter, Subfamily G, Member 2
/ biosynthesis
Acetylation
/ drug effects
Animals
Brain
/ metabolism
Gene Expression Regulation
/ drug effects
Histone Deacetylase Inhibitors
/ pharmacology
Histone Deacetylases
/ metabolism
Histones
/ metabolism
Male
Mice
Peptides, Cyclic
/ pharmacology
Valproic Acid
/ pharmacology
Abcb1
Abcg2
P-glycoprotein
brain
breast cancer resistance protein (BCRP)
histone deacetylase (HDAC) inhibitor
multidrug resistance protein 1 (MDR1)
transporter
Journal
Journal of biochemical and molecular toxicology
ISSN: 1099-0461
Titre abrégé: J Biochem Mol Toxicol
Pays: United States
ID NLM: 9717231
Informations de publication
Date de publication:
Jun 2019
Jun 2019
Historique:
received:
21
12
2018
revised:
12
02
2019
accepted:
19
02
2019
pubmed:
22
3
2019
medline:
6
8
2020
entrez:
22
3
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 30897286
doi: 10.1002/jbt.22318
pmc: PMC6754812
mid: NIHMS1013746
doi:
Substances chimiques
ATP Binding Cassette Transporter, Subfamily B, Member 1
0
ATP Binding Cassette Transporter, Subfamily G, Member 2
0
Abcg2 protein, mouse
0
Histone Deacetylase Inhibitors
0
Histones
0
Peptides, Cyclic
0
apicidin
0
Valproic Acid
614OI1Z5WI
Histone Deacetylases
EC 3.5.1.98
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e22318Subventions
Organisme : National Institutes of Health
Organisme : NIEHS NIH HHS
ID : P30 ES005022
Pays : United States
Organisme : NIEHS NIH HHS
ID : R01 ES021800
Pays : United States
Organisme : National Institute of Environmental Health Sciences
ID : P30ES005022
Organisme : National Institute of Environmental Health Sciences
ID : R01ES021800
Informations de copyright
© 2019 Wiley Periodicals, Inc.
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