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Suberoylanilide hydroxamic acid induces limited changes in the transcriptome of primary CD4(+) T cells.
- Source :
-
AIDS (London, England) [AIDS] 2013 Jan 02; Vol. 27 (1), pp. 29-37. - Publication Year :
- 2013
-
Abstract
- Objective: To assess the off-target effects of the histone deacetylase inhibitor (HDACi) suberoylanilide hydroxamic acid (SAHA) in human primary CD4 T cells.<br />Design: A pharmacologically relevant concentration (340 nmol/l) of SAHA was shown to significantly increase histone hyperacetylation by 24 h and this length of treatment was selected to determine its impact on gene expression in primary CD4 T cells.<br />Methods: Illumina Beadchips for microarray gene expression analysis were used to analyze differential gene expression between cells treated or not with SAHA with a paired analysis using multivariate permutation tests. Gene ontology, biological pathway and protein interaction network analyses were used to identify the higher order biological processes affected by SAHA treatment.<br />Results: Modest modulation by SAHA was observed for 1847 genes with 80% confidence level of no more than 10% false positives. A thousand genes were upregulated by SAHA and 847 downregulated. Pathways and gene ontologies overrepresented in the list of differentially expressed genes included Glycolysis/Gluconeogenesis, tRNA Modification, and the Histone Acetyltransferase Complex. Protein interaction network analysis revealed that transcription factor c-Myc, which was downregulated by SAHA treatment at the mRNA level, interacts with a number of SAHA-responsive genes.<br />Conclusions: The effects on transcription by SAHA were sufficiently modest to support trials to activate HIV replication as part of an eradication strategy. SAHA did not appear to modulate proliferative or apoptotic processes to a great extent, which might impact the ability of patients to eradicate the virus reservoir following activation by HDACi treatment.
- Subjects :
- Apoptosis drug effects
CD4-Positive T-Lymphocytes metabolism
Female
Gene Expression Regulation, Viral drug effects
Humans
Male
Real-Time Polymerase Chain Reaction
Virus Replication drug effects
Vorinostat
CD4-Positive T-Lymphocytes drug effects
Cell Proliferation drug effects
HIV-1 drug effects
Histone Deacetylase Inhibitors pharmacology
Hydroxamic Acids pharmacology
Transcriptome drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1473-5571
- Volume :
- 27
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- AIDS (London, England)
- Publication Type :
- Academic Journal
- Accession number :
- 23221426
- Full Text :
- https://doi.org/10.1097/QAD.0b013e32835b3e26