title: Apoptotic effect of ethanol is potentiated by caffeine-induced calcium release in rat astrocytes.
abstract: In this study, we investigated agents that increased intracellular calcium levels and their correlation with apoptotic cell death induction. We used rat astrocytes to investigate the increase in cytosolic Ca2+ (Ca(c)2+) and apoptosis induction by drugs that mobilize Ca2+ from different sources. We observed that thapsigargin (Thap), caffeine (Caff) and FCCP which caused similar increases in Ca(c)2+ levels (30-40%), also induced similar apoptotic rates (30-35%). On the other hand, antimycin (Anti), staurosporine (STS) and ethanol (Eth) promoted higher increases in Ca(c)2+ (55-65 %) and higher apoptotic rates (55-85%). Eth induced cell death in a concentration- and time-dependent manner. After treatment with Eth plus Caff for 6, 12 and 24 h, these effects were strongly potentiated. Results suggest that there might be a correlation between Ca(c)2+ increase and the rate of apoptosis. It is possible that Eth induces cell death by activation of more than one pathway and Ca2+ might be one of the elements involved. The present work indicates that Ca2+ can potentiate death by ethanol in rat astrocytes.
authors.affiliation: Department of Pharmacology, Federal University of São Paulo, School of Medicine, Rua Três de Maio, 100, São Paulo SP 04044-020, Brazil.
authors.forename: Hanako
authors.initials: H
authors.lastname: Hirata
authors.forename: Lucas S
authors.initials: LS
authors.lastname: Machado
authors.forename: Clayton S
authors.initials: CS
authors.lastname: Okuno
authors.forename: Adriano
authors.initials: A
authors.lastname: Brasolin
authors.forename: Guiomar S
authors.initials: GS
authors.lastname: Lopes
authors.forename: Soraya S
authors.initials: SS
authors.lastname: Smaili
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017304:Annexin A5 / Q000378:metabolism; D000968:Antimycin A / Q000031:analogs & derivatives / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D002110:Caffeine / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology; D002478:Cells, Cultured; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D002712:Chlorides / Q000494:pharmacology; D004072:Digitonin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology*; D005434:Flow Cytometry / Q000379:methods; D016257:Fura-2; D020287:In Situ Nick-End Labeling / Q000379:methods; D007202:Indicators and Reagents / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D017895:Manganese Compounds / Q000494:pharmacology; D011419:Propidium / Q000378:metabolism; D051381:Rats; D019311:Staurosporine / Q000494:pharmacology; D019284:Thapsigargin / Q000494:pharmacology; D013997:Time Factors
chemical_list: D017304:Annexin A5; D002492:Central Nervous System Depressants; D000697:Central Nervous System Stimulants; D002712:Chlorides; D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D007476:Ionophores; D017895:Manganese Compounds; C032456:antimycin; D011419:Propidium; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; D002110:Caffeine; D000431:Ethanol; D000968:Antimycin A; D019284:Thapsigargin; D019311:Staurosporine; D004072:Digitonin; C025340:manganese chloride; D002118:Calcium; D016257:Fura-2