Organotin compounds induce calcium overload and apoptosis in PC12 cells.
We examined the effects of four tri-substituted organotin compounds on intracellular Ca2+ and survival in PC12 cells. Treatment with micromolar concentrations of tributyltin and triphenyltin caused a rapid increase in the cytosolic free Ca2+ concentration ([Ca2+]i). This was due to enhanced Ca2+ influx and release from intracellular stores. When the [Ca2+]i elevation was maintained for over 30 min, internucleosomal DNA cleavage typical of apoptotic cell death followed. In contrast, when the increase in [Ca2+]i was transient, cells did not show internucleosomal DNA cleavage and retained their viability. Triethyltin modified [Ca2+]i only slightly, whereas trimethyltin had no effect. The latter two agents did not modify cell viability. Our data suggest that the toxicity of organotins in PC12 cells is linked to their ability to promote intracellular Ca2+ overload, which triggers apoptosis.
Viviani
B
B
Division of Toxicology, Karolinska Institute, Stockholm, Sweden.
Rossi
A D
AD
Chow
S C
SC
Nicotera
P
P
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism*; D015342:DNA Probes; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009947:Organotin Compounds / Q000494:pharmacology*; D016716:PC12 Cells; D051381:Rats; D014220:Trialkyltin Compounds / Q000494:pharmacology
D015342:DNA Probes; D009947:Organotin Compounds; D014220:Trialkyltin Compounds; C011559:tributyltin; D004533:Egtazic Acid; C030665:triphenyltin; D002118:Calcium