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

Authors

Marisela Agudelo, Herbert Wertheim College of Medicine, Florida International UniversityFollow
Gloria Figueroa, Herbert Wertheim College of Medicine, Florida International UniversityFollow
Tiyash Parira, Herbert Wertheim College of Medicine, Florida International UniversityFollow
Adriana Yndart, Herbert Wertheim College of Medicine, Florida International UniversityFollow
Karla Munoz, Herbert Wertheim College of Medicine, Florida International UniversityFollow
Venkata Atluri, Herbert Wertheim College of Medicine, Florida International UniversityFollow
Thangavel Samikkannu, Herbert Wertheim College of Medicine, Florida International University
Madhavan P. Nair, Herbert Wertheim College of Medicine, Florida International UniversityFollow

Date of this Version

6-1-2016

Document Type

Article

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.

Originally Published In

PLoS ONE

PMID

27249803

DOI

10.1371/journal.pone.0156421

Recommended Citation

Agudelo, Marisela; Figueroa, Gloria; Parira, Tiyash; Yndart, Adriana; Munoz, Karla; Atluri, Venkata; Samikkannu, Thangavel; and Nair, Madhavan P., "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" (2016). All Faculty. 129.
https://digitalcommons.fiu.edu/all_faculty/129

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 License.