title: Ethanol promotes T cell apoptosis through the mitochondrial pathway.
abstract: Clinical reports suggest that acute ethanol intoxication is often associated with lymphopenia. Previously, ethanol was reported to invoke thymocyte apoptosis. We studied the effect of ethanol on T cell apoptosis. In addition, we evaluated the molecular mechanism of ethanol-induced T cell apoptosis. Human T cells harvested from healthy subjects after an alcohol drinking binge showed enhanced T cell apoptosis (before, 0.4 +/- 0.2% versus after, 19.6 +/- 2.5% apoptotic lymphocytes/field; P < 0.001). In in vitro studies, ethanol in a concentration of 50 mm and higher enhanced the apoptosis of Jurkat cells. DNA isolated from ethanol-treated Jurkat cells displayed integer multiples of 180 base pairs. Ethanol decreased Jurkat cell expression of Bcl-2, whereas ethanol increased Jurkat cell expression of Bax. Jurkat cells treated with ethanol also showed translocation of cytochrome C into cytosol. Moreover, a caspase-9 inhibitor partially inhibited ethanol-induced Jurkat cell apoptosis. In in vivo studies, after binge drinking, T cell expression of Bcl-2 also decreased. In addition, binge drinking induced the cleavage of caspase-3, suggesting activation of caspase-3 in T cells. These results suggest that ethanol promotes T cell apoptosis through the activation of intrinsic or mitochondrial pathway.
authors.affiliation: Department of Medicine, Long Island Jewish Medical Center, New Hyde Park, NY 11040, USA.
authors.forename: Aditi A
authors.initials: AA
authors.lastname: Kapasi
authors.forename: Geeta
authors.initials: G
authors.lastname: Patel
authors.forename: Anuj
authors.initials: A
authors.lastname: Goenka
authors.forename: Nilay
authors.initials: N
authors.lastname: Nahar
authors.forename: Neeraj
authors.initials: N
authors.lastname: Modi
authors.forename: Madhu
authors.initials: M
authors.lastname: Bhaskaran
authors.forename: Krishna
authors.initials: K
authors.lastname: Reddy
authors.forename: Nicholas
authors.initials: N
authors.lastname: Franki
authors.forename: Jaimita
authors.initials: J
authors.lastname: Patel
authors.forename: Pravin C
authors.initials: PC
authors.lastname: Singhal
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D020169:Caspases / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology* / Q000506:poisoning; D006801:Humans; D019169:Jurkat Cells; D008297:Male; D008928:Mitochondria / Q000187:drug effects*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D051028:bcl-2-Associated X Protein
chemical_list: C494826:BAX protein, human; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D000431:Ethanol; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases