title: The effect of histone deacetylase inhibition on the expression of P-glycoprotein in human placental trophoblast cell lines.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  HDACs inhibition could up-regulate placental P-gp expression in trophoblast cells, and HDAC1/2 was most likely to be involved in this process.
authors.affiliation: 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.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Duan
authors.affiliation: 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.
authors.forename: Chuan
authors.initials: C
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Kaiyu
authors.initials: K
authors.lastname: Zhou
authors.affiliation: 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.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Yifei
authors.initials: Y
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Dajian
authors.initials: D
authors.lastname: Qiu
authors.affiliation: Department of Pediatric Hematology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Yimin
authors.initials: Y
authors.lastname: Hua
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D002460:Cell Line; D005260:Female; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D011247:Pregnancy; D014327:Trophoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000077337:Vorinostat
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; C012589:trichostatin A; D000077337:Vorinostat; D006655:Histone Deacetylases
keywords: Epigenetic regulation; HDACs; P-glycoprotein; Placenta