title: Effects of Histone Deacetylase Inhibitor (Valproic Acid) on the Expression of Hypoxia-inducible Factor-1 Alpha in Human Retinal Müller Cells.
abstract: OBJECTIVE
  To evaluate the effects of valproic acid (VPA), a histone deacetylase inhibitor (HDACI), on the expression of hypoxia-inducible factor-1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF) in human retinal Müller cells under hypoxic conditions.
  
  
  METHODS
  Chemical hypoxia was induced in human retinal Müller cells (MIO-M1) by treatment with increasing concentrations of cobalt(II) chloride (CoCl2). Müller cells were also treated with a set concentration of CoCl2, along with various concentrations of VPA. The expression of HIF-1α and VEGF in the treated Müller cells was determined by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  Exposure of human retinal Müller cells to increasing concentrations of CoCl2produced a dose-dependent increase in HIF-1α expression. The addition of increasing concentrations of VPA lead to a dose-dependent decrease in expression of HIF-1α and VEGF in Müller cells exposed to a set concentration of CoCl2.
  
  
  CONCLUSIONS
  HDACI VPA downregulated the expressions of HIF-1α and VEGF in human retinal Müller cells under hypoxic conditions. Using HDACI to target HIF-1α expression in Müller cells could be a new therapeutic strategy for the treatment of retinal vascular diseases.
authors.affiliation: Department of Ophthalmology and Inha Vision Science Laboratory, Inha University School of Medicine, Incheon, Korea.
authors.forename: Young Jun
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Department of Ophthalmology and Inha Vision Science Laboratory, Inha University School of Medicine, Incheon, Korea.
authors.forename: Sang Jun
authors.initials: SJ
authors.lastname: Park
authors.affiliation: Department of Ophthalmology and Inha Vision Science Laboratory, Inha University School of Medicine, Incheon, Korea.
authors.forename: Na Rae
authors.initials: NR
authors.lastname: Kim
authors.affiliation: Department of Ophthalmology and Inha Vision Science Laboratory, Inha University School of Medicine, Incheon, Korea.
authors.forename: Hee Seung
authors.initials: HS
authors.lastname: Chin
mesh_terms: D002460:Cell Line; D002470:Cell Survival; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D063928:Ependymoglial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis*; D014635:Valproic Acid / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D014635:Valproic Acid
keywords: Histone deacetylase inhibitors; Hypoxia-inducible factor 1 alpha; Retinal Muller cells; Valproic acid; Vascular endothelial growth factor