THE S-100 PROTEIN CAUSES AN INCREASE OF INTRACELLULAR CALCIUM AND DEATH OF PC12 CELLS

The S-100 protein-PC12 cell interaction has been studied as a model sy stem of the possible physiological role played by S-100 protein in the nervous system. The data reported demonstrate that S-100 exerts a cyt otoxic action which eventually leads to PC12 cell death, regardless of the cell cycle phase. The effect is specific for the S-100 isoforms, which are made up of two identical subunits and is abolished by a mono clonal antibody directed against the same isoforms. Other isoforms and /or calcium-binding proteins, such as troponin or calmodulin, do not i nduce the same effects. The action of S-100 on cell viability is not d etectable in other cell lines of different embryological origin, such as 3T3, L1210, GH3. S-100 causes a rapid and considerable increase (tw o- to three-fold) of intracellular Ca2+ concentration in PC12 cells ac companied by cytostatic and cytotoxic action. It is postulated that th is action also occurs in vivo, as part of the physiological action of this protein.