Regulation of signal transduction and DNA fragmentation in thymocytes by ethanol.
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.
Shao
H
H
Department of Pathobiology, Auburn University, Alabama 36849-5519, USA.
Zhou
J
J
Ewald
S J
SJ
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
D005576:Colforsin; D000431:Ethanol; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D007545:Isoproterenol; D002118:Calcium