title: 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.
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.
authors.affiliation: Department of Immunology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, United States of America.|Institute on NeuroImmune Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, United States of America.
authors.forename: Marisela
authors.initials: M
authors.lastname: Agudelo
authors.affiliation: Department of Immunology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, United States of America.
authors.forename: Gloria
authors.initials: G
authors.lastname: Figueroa
authors.affiliation: Department of Immunology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, United States of America.
authors.forename: Tiyash
authors.initials: T
authors.lastname: Parira
authors.affiliation: Department of Immunology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, United States of America.|Institute on NeuroImmune Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, United States of America.
authors.forename: Adriana
authors.initials: A
authors.lastname: Yndart
authors.affiliation: Department of Immunology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, United States of America.|Institute on NeuroImmune Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, United States of America.
authors.forename: Karla
authors.initials: K
authors.lastname: Muñoz
authors.affiliation: Department of Immunology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, United States of America.|Institute on NeuroImmune Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, United States of America.
authors.forename: Venkata
authors.initials: V
authors.lastname: Atluri
authors.affiliation: Department of Immunology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, United States of America.|Institute on NeuroImmune Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, United States of America.
authors.forename: Thangavel
authors.initials: T
authors.lastname: Samikkannu
authors.affiliation: Department of Immunology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, United States of America.|Institute on NeuroImmune Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, United States of America.
authors.forename: Madhavan P
authors.initials: MP
authors.lastname: Nair
mesh_terms: D000428:Alcohol Drinking; D000975:Antioxidants / Q000378:metabolism; D001549:Benzamides / Q000494:pharmacology*; D003713:Dendritic Cells / Q000187:drug effects* / Q000201:enzymology; D005260:Female; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D018384:Oxidative Stress; D011743:Pyrimidines / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000975:Antioxidants; D001549:Benzamides; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D011743:Pyrimidines; D017382:Reactive Oxygen Species; C012589:trichostatin A; C523184:mocetinostat; D006655:Histone Deacetylases