Nerve growth factor- and non-stimulated PC12 cells as models for sympathetic ganglion neurons and adrenal chromaffin cells

Abstract PC12 cells are an immortalized cell line originating from rat adrenal medullary chromaffin (AMC) cells and extend a neurite-like structure in response to nerve growth factor (NGF). Thus, non-stimulated and NGF-stimulated PC12 cells are used as model cells for AMC cells and sympathetic ganglion cells, respectively. However, how closely non-stimulated and stimulated PC12 cells resemble AMC cells and sympathetic neurons, respectively, has not sufficiently been elucidated. In addition, how the properties of PC12 cells are affected by NGF remains unclear. These issues were explored by using biochemical and immunocytochemical methods. AMC cells and PC12 cells selectively expressed UCP3 and UCP4, respectively, key proteins which are involved in energy metabolism in a cell-specific manner, and glucocorticoid activity exerted an inhibitory effect on UCP4 expression in PC12 cells. The expression levels of chromaffin granule-associated proteins in PC12 cells were extremely small, whereas the amount of synaptophysin, a synaptic vesicle-associated protein, was much larger than that in the adrenal medulla. As found in AMC cells, the muscarinic receptor subtype 1 (M1R) were located at the cell periphery in basal PC12 cells, as was markedly enhanced by NGF. Furthermore, the proteins involved in GABA auto/paracrine function in AMC cells were expressed in non-stimulated PC12 cells, but not in NGF-stimulated cells. The results suggest that the properties of basal PC12 cells are between those of AMC cells and sympathetic ganglion cells, and glucocorticoid activity and NGF induce differentiation into AMC cells and sympathetic neurons, respectively, and GABA functions as an auto/paracrine factor in AMC cells.