title: Regulation of signal transduction and DNA fragmentation in thymocytes by ethanol.
abstract: We demonstrated previously that ethanol enhances apoptosis of murine thymocytes. In this report, we determined intracellular cAMP and cytosolic free calcium ([Ca2+]i) levels in mouse thymocytes following acute exposure to ethanol and investigated the involvement of cAMP, [Ca2+]i, protein kinase A (PKA), and protein kinase C (PKC) in thymocyte apoptotic death induced by ethanol. It was found that ethanol did not alter basal cAMP levels, but produced a dose-dependent, prolonged small [Ca2+]i increase within thymocytes. This dose dependence of [Ca2+]i increase was paralleled by the magnitude of DNA fragmentation induced by ethanol at various concentrations. Additionally, the ethanol-enhanced DNA fragmentation was blocked by H7, a PKC inhibitor, but not by potent PKA inhibitors having little or no effect on PKC. These data suggest that both [Ca2+]i increase and PKC activation triggered by ethanol may belong to the signal pathway(s) leading to thymocyte programmed death.
authors.affiliation: Department of Pathobiology, Auburn University, Alabama 36849-5519, USA.
authors.forename: H
authors.initials: H
authors.lastname: Shao
authors.forename: J
authors.initials: J
authors.lastname: Zhou
authors.forename: S J
authors.initials: SJ
authors.lastname: Ewald
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000037:antagonists & inhibitors / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology / Q000633:toxicity; D000242:Cyclic AMP / Q000037:antagonists & inhibitors; D017868:Cyclic AMP-Dependent Protein Kinases / Q000187:drug effects; D003600:Cytosol / Q000737:chemistry; D004249:DNA Damage / Q000276:immunology*; D000431:Ethanol / Q000494:pharmacology* / Q000633:toxicity*; D005470:Fluorometry; D007545:Isoproterenol / Q000494:pharmacology / Q000633:toxicity; D051379:Mice; D008810:Mice, Inbred C57BL; D011493:Protein Kinase C / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects*; D013601:T-Lymphocytes / Q000187:drug effects; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects
chemical_list: D005576:Colforsin; D000431:Ethanol; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D007545:Isoproterenol; D002118:Calcium