The effect of histone deacetylase inhibitors on AHSP expression
| Autor: | Reza Ranjbaran, Negin Nikouyan, Mohammad Ali Okhovat, Katayoun Ziari |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Gene Expression lcsh:Medicine Biochemistry Histones Gene expression STAT3 lcsh:Science Multidisciplinary biology Chemistry GATA1 Sodium phenylbutyrate Blood Proteins Phenylbutyrates Nucleic acids Real-time polymerase chain reaction Physical Sciences Hyperexpression Techniques Research Article medicine.drug Gene isoform Nucleic acid synthesis Sodium DNA transcription chemistry.chemical_element Real-Time Polymerase Chain Reaction Research and Analysis Methods Kruppel-Like Factor 4 03 medical and health sciences DNA-binding proteins Genetics Gene Expression and Vector Techniques medicine Humans Gene Regulation Chemical synthesis RNA synthesis Molecular Biology Techniques Molecular Biology Molecular Biology Assays and Analysis Techniques Biology and life sciences Valproic Acid lcsh:R Chemical Compounds Proteins Molecular biology Regulatory Proteins Hemoglobinopathies Histone Deacetylase Inhibitors Biosynthetic techniques 030104 developmental biology Gene Expression Regulation biology.protein RNA Salts lcsh:Q Histone deacetylase K562 Cells Molecular Chaperones Transcription Factors |
| Zdroj: | PLoS ONE, Vol 13, Iss 2, p e0189267 (2018) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | Alpha-hemoglobin stabilizing protein (AHSP) is a molecular chaperone that can reduce the damage caused by excess free α-globin to erythroid cells in patients with impaired β-globin chain synthesis. We assessed the effect of sodium phenylbutyrate and sodium valproate, two histone deacetylase inhibitors (HDIs) that are being studied for the treatment of hemoglobinopathies, on the expression of AHSP, BCL11A (all isoforms), γ-globin genes (HBG1/2), and some related transcription factors including GATA1, NFE2, EKLF, KLF4, and STAT3. For this purpose, the K562 cell line was cultured for 2, 4, and 6 days in the presence and absence of sodium phenylbutyrate and sodium valproate. Relative real-time qRT-PCR analysis of mRNA levels was performed to determine the effects of the two compounds on gene expression. Expression of all target mRNAs increased significantly (p < 0.05), except for the expression of BCL11A, which was down-regulated (p < 0.05) in the cells treated with both compounds relative to the levels measured for untreated cells. The findings indicated that sodium valproate had a more considerable effect than sodium phenylbutyrate (p < 0.0005) on BCL11A repression and the up-regulation of other studied genes. γ-Globin and AHSP gene expression continuously increased during the culture period in the treated cells, with the highest gene expression observed for 1 mM sodium valproate after 6 days. Both compounds repressed the expression of BCL11A (-XL, -L, -S) and up-regulated GATA1, NFE2, EKLF, KLF4, STAT3, AHSP, and γ-globin genes expression. Moreover, sodium valproate showed a stronger effect on repressing BCL11A and escalating the expression of other target genes. The findings of this in vitro experiment could be considered in selecting drugs for clinical use in patients with β-hemoglobinopathies. |
| Databáze: | OpenAIRE |
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