Apoptotic effect of ethanol is potentiated by caffeine-induced calcium release in rat astrocytes.
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.
Hirata
Hanako
H
Department of Pharmacology, Federal University of São Paulo, School of Medicine, Rua Três de Maio, 100, São Paulo SP 04044-020, Brazil.
Machado
Lucas S
LS
Okuno
Clayton S
CS
Brasolin
Adriano
A
Lopes
Guiomar S
GS
Smaili
Soraya S
SS
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
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