Calcium and Fos involvement in brain-derived Ca2+-binding protein (S100)-dependent apoptosis in rat phaeochromocytoma cells

Brain-derived calcium-binding protein S100 induces apoptosis in a significa nt fraction of rat phaeochromocytoma (PC12) cells. We used single cell tech niques (patch clamp, videomicroscopy and immunocytochemistry) to clarify so me of the specific aspects of S100-induced apoptosis, the modality(ies) of early intracellular Ca2+ concentration increase and the expression of some classes of genes (c-fos, c-jun, bax, bcl-x, p-15, p-21) known to be implica ted in apoptosis of different cells. The results show that S100: (1) causes an increase of [Ca2+](i) due to an increased conductance of L-type Ca2+ ch annels; (2) induces a sustained increase of the Fos levels which is evident since the first time point tested (3 h) and remains elevated until to the last time point (72 h). All these data suggest that S100-derived apoptosis in PC12 cells may be the consequence of a system involving an increase in L -type Ca2+ channel conductance with consequent [Ca2+](i) increase which up- regulates, directly or indirectly, the expression of Fos.