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

被引:9
作者
Agudelo, Marisela [1 ,2 ]
Figueroa, Gloria [1 ]
Parira, Tiyash [1 ]
Yndart, Adriana [1 ,2 ]
Munoz, Karla [1 ,2 ]
Atluri, Venkata [1 ,2 ]
Samikkannu, Thangavel [1 ,2 ]
Nair, Madhavan P. [1 ,2 ]
机构
[1] Florida Int Univ, Dept Immunol, Herbert Wertheim Coll Med, Miami, FL 33199 USA
[2] Florida Int Univ, Inst NeuroImmune Pharmacol, Herbert Wertheim Coll Med, Miami, FL 33199 USA
关键词
DISORDERS IDENTIFICATION TEST; GENE-EXPRESSION; COMBINATION; MECHANISMS; RESPONSES; DRINKING; RATS;
D O I
10.1371/journal.pone.0156421
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];
摘要
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.
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页数:19
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