Profile of Class I Histone Deacetylases (HDAC) by Human Dendritic Cells after Alcohol Consumption and In Vitro Alcohol Treatment and Their Implication in Oxidative Stress: Role of HDAC Inhibitors Trichostatin A and Mocetinostat
Open Access
- 1 June 2016
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 11 (6), e0156421
- https://doi.org/10.1371/journal.pone.0156421
Abstract
Epigenetic mechanisms have been shown to play a role in alcohol use disorders (AUDs) and may prove to be valuable therapeutic targets. However, the involvement of histone deacetylases (HDACs) on alcohol-induced oxidative stress of human primary monocyte-derived dendritic cells (MDDCs) has not been elucidated. In the current study, we took a novel approach combining ex vivo, in vitro and in silico analyses to elucidate the mechanisms of alcohol-induced oxidative stress and role of HDACs in the periphery. ex vivo and in vitro analyses of alcohol-modulation of class I HDACs and activity by MDDCs from self-reported alcohol users and non-alcohol users was performed. Additionally, MDDCs treated with alcohol were assessed using qRT-PCR, western blot, and fluorometric assay. The functional effects of alcohol-induce oxidative stress were measured in vitro using PCR array and in silico using gene expression network analysis. Our findings show, for the first time, that MDDCs from self-reported alcohol users have higher levels of class I HDACs compare to controls and alcohol treatment in vitro differentially modulates HDACs expression. Further, HDAC inhibitors (HDACi) blocked alcohol-induction of class I HDACs and modulated alcohol-induced oxidative stress related genes expressed by MDDCs. In silico analysis revealed new target genes and pathways on the mode of action of alcohol and HDACi. Findings elucidating the ability of alcohol to modulate class I HDACs may be useful for the treatment of alcohol-induced oxidative damage and may delineate new potential immune-modulatory mechanisms.Funding Information
- National Institute on Alcohol Abuse and Alcoholism (R00 AA021264)
- National Institute on Drug Abuse (R01DA034547)
This publication has 40 references indexed in Scilit:
- Chromatin remodeling — a novel strategy to control excessive alcohol drinkingTranslational Psychiatry, 2013
- Ethanol Concentration‐Dependent Alterations in Gene Expression During Acute Binge Drinking in the HIV ‐1 Transgenic RatAlcohol: Clinical and Experimental Research, 2013
- Combination of HDAC and topoisomerase inhibitors in small cell lung cancerCancer Biology & Therapy, 2012
- HIV-1 Tat upregulates expression of histone deacetylase-2 (HDAC2) in human neurons: Implication for HIV-associated neurocognitive disorder (HAND)Neurochemistry International, 2011
- Effects of Alcohol on Histone Deacetylase 2 (HDAC2) and the Neuroprotective Role of Trichostatin A (TSA)Alcohol: Clinical and Experimental Research, 2011
- Dendritic Cells in Alcoholic Liver Injury and FibrosisAlcohol: Clinical and Experimental Research, 2011
- Autophagic and Apoptotic Effects of HDAC Inhibitors on Cancer CellsJournal of Biomedicine and Biotechnology, 2011
- Histone deacetylase inhibitors: Potential in cancer therapyJournal of Cellular Biochemistry, 2009
- Mechanism of alcohol-induced oxidative stress and neuronal injuryFree Radical Biology & Medicine, 2008
- The Alcohol Use Disorders Identification Test: An Update of Research FindingsAlcohol: Clinical and Experimental Research, 2007