The brain protein S-100ab induces apoptosis in PC12 cells.
Incubation of PC12 cells with S-100 protein induces a rapid (0.5-1.0 min) rise of intracellular Ca2+ which lasts for the whole period of incubation. This effect is abolished in a Ca(2+)-free medium or in the presence of 1.0 microM Ni2+, an inhibitor of calcium channels. The rise in intracellular Ca2+ is followed by a progressive increase of cells undergoing degeneration and death. This event is accompanied by the appearance of apoptotic bodies and DNA fragmentation typical of the process known as apoptosis. S-100-induced cell death is prevented by 1 microM Ni2+ or by 0.1 nM cycloheximide, suggesting the involvement of new protein synthesis. It is postulated that the binding of S-100ab to specific sites present in PC12 cells is followed by the formation of Ca2+ channels and/or the stimulation of pre-existing ones with consequent increase of Ca2+ influx and activation of a process of cell death.
Mariggió
M A
MA
Istituto di Biologia Cellulare, CNR, Roma, Italy.
Fulle
S
S
Calissano
P
P
Nicoletti
I
I
Fanó
G
G
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D003513:Cycloheximide / Q000494:pharmacology; D004273:DNA, Neoplasm / Q000302:isolation & purification; D004591:Electrophoresis, Polyacrylamide Gel; D009532:Nickel / Q000494:pharmacology; D016716:PC12 Cells; D051381:Rats; D009418:S100 Proteins / Q000037:antagonists & inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D013194:Staining and Labeling
D004273:DNA, Neoplasm; D009418:S100 Proteins; D009532:Nickel; D003513:Cycloheximide; D002118:Calcium