The effect of histone deacetylase inhibition on the expression of P-glycoprotein in human placental trophoblast cell lines

Hongyu Duan; Chuan Wang; Kaiyu Zhou; Tao Wang; Yifei Li; Dajian Qiu; Qiang Li; Yi Zhang; Yimin Hua

doi:10.1016/j.placenta.2016.11.011

The effect of histone deacetylase inhibition on the expression of P-glycoprotein in human placental trophoblast cell lines

Placenta. 2017 Jan:49:37-47. doi: 10.1016/j.placenta.2016.11.011. Epub 2016 Nov 23.

Authors

Hongyu Duan¹, Chuan Wang², Kaiyu Zhou³, Tao Wang¹, Yifei Li², Dajian Qiu⁴, Qiang Li⁵, Yi Zhang⁶, Yimin Hua⁷

Affiliations

¹ Department of Pediatric Cardiology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China; The Cardiac Development and Early Intervention Unit, West China Institute of Women and Children's Health, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China; West China Medical School of Sichuan University, Chengdu, Sichuan, China.
² Department of Pediatric Cardiology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China; The Cardiac Development and Early Intervention Unit, West China Institute of Women and Children's Health, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China.
³ Department of Pediatric Cardiology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China; The Cardiac Development and Early Intervention Unit, West China Institute of Women and Children's Health, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China; Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, Sichuan, China.
⁴ The Cardiac Development and Early Intervention Unit, West China Institute of Women and Children's Health, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China.
⁵ Department of Pediatric Hematology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China.
⁶ The Cardiac Development and Early Intervention Unit, West China Institute of Women and Children's Health, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China; Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, Sichuan, China. Electronic address: 349777010@qq.com.
⁷ Department of Pediatric Cardiology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China; The Cardiac Development and Early Intervention Unit, West China Institute of Women and Children's Health, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China; Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, Sichuan, China. Electronic address: nathan_hua@126.com.

PMID: 28012453
DOI: 10.1016/j.placenta.2016.11.011

Abstract

Introductions: Placental P-glycoprotein (P-gp), encoded by ABCB1 gene in human, plays a significant role in regulating drugs' transplacental transfer rates. Investigations on placental P-gp regulation could provide more therapeutic targets for individualized and safe pharmacotherapy during pregnancy. Currently, the epigenetic control of placental P-gp is rare. This study aimed to investigate the effect of histone deacetylases (HDACs) inhibition on P-gp expression in placental trophoblast cell lines and to explore whether HDAC1/2/3 was involved in this process preliminarily.

Methods: Human placental trophoblast cell lines (Bewo and JAR) were treated with two different HDAC inhibitors-suberoylanilide hydroxamic acid (SAHA) and trichostatin A (TSA) at different concentration gradients of 0.5, 1.0, 3.0 and 5.0 μM. Cells were harvested after 24, 48, and 72 h treatment. Total HDAC activity was detected by colorimetric assay Kits. HDAC1/2/3/ABCB1 mRNA and protein expressions were determined by real-time quantitative PCR and western-blot, respectively. Pearson correlation analysis test was performed to explore the relationship between HDAC1/2/3 mRNA and ABCB1 mRNA expression.

Results: SAHA and TSA could inhibit total HDAC activity and placental HDAC1/2/3 expression both in Bewo and JAR, but displayed a transient induction of HDAC mRNA or protein level after being treated at low dosage or prolonged exposure to drugs. Discordance in HDAC mRNA and protein expression was also observed. Placental P-gp expression was significantly induced in company with HDACs inhibition. There was a significant negative linear relationship between HDAC1/2 mRNA and ABCB1 mRNA expression.

Conclusions: HDACs inhibition could up-regulate placental P-gp expression in trophoblast cells, and HDAC1/2 was most likely to be involved in this process.

Keywords: Epigenetic regulation; HDACs; P-glycoprotein; Placenta.

MeSH terms

ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
Cell Line
Female
Histone Deacetylase Inhibitors / pharmacology*
Histone Deacetylases / metabolism*
Humans
Hydroxamic Acids / pharmacology
Pregnancy
Trophoblasts / cytology
Trophoblasts / drug effects*
Trophoblasts / metabolism
Vorinostat

Substances

ATP Binding Cassette Transporter, Subfamily B, Member 1
Histone Deacetylase Inhibitors
Hydroxamic Acids
trichostatin A
Vorinostat
Histone Deacetylases