INDUCTION OF CALBINDIN-D 28K GENE AND PROTEIN EXPRESSION BY PHYSIOLOGICAL STIMULI BUT NOT IN CALCIUM-MEDIATED DEGENERATION IN RAT PC12 PHEOCHROMOCYTOMA CELLS

To understand the role of calbindin-D 28K in neuronal degeneration, we examined its expression in differentiated PC12 cells in response to c alcium intoxication, using the ionophore A23187 treatment, that result s in cell degeneration and death. We first established that calbindin- D 28K is expressed in PC12 cells. The amounts of calbindin-D 28K mRNA and protein were increased by the differentiation factors, NGF and ret inoic acid, but not by vitamin D-3. Calbindin-D 28K expression was als o significantly up-regulated by stimuli (depolarization, low concentra tions of Ca2+ ionophore A23187) which increase intracellular calcium l evels within the physiological range. In contrast, the calbindin-D 28K mRNA and protein concentrations were not modulated by high concentrat ions of A23187, which resulted in cell degeneration and death. Experim ents with the antisense oligonucleotides showed that, although the cal bindin-D 28K protein levels were decreased significantly, the progress ion of degenerative changes induced by calcium via A23187, was not alt ered.