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 m in) rise of intracellular Ca2+ which lasts for the whole period of inc ubation. This effect is abolished in a Ca2+-free medium or in the pres ence of 1.0 mu M Ni2+, an inhibitor of calcium channels. The rise in i ntracellular Ca2+ is followed by a progressive increase of cells under going degeneration and death. This event is accompanied by the appeara nce of apoptotic bodies and DNA fragmentation typical of the process k nown as apoptosis. S-100-induced cell death is prevented by 1 mu M Ni2 + or by 0.1 nM cycloheximide, suggesting the involvement of new protei n synthesis. It is postulated that the binding of S-100ab to specific sites present in PC12 cells is followed by the formation of Ca2+ chann els and/or the stimulation of pre-existing ones with consequent increa se of Ca2+ influx and activation of a process of cell death.