Dual effect of nerve growth factor on cell death of PC12 cells induced by serum deprivation

The effect of nerve growth factor (NGF) on the cell death of PC12 cells that is induced by serum deprivation was examined in the floating and attached cells to the extracellular matrix. NGF suppressed cell death occurred in the floating cells. The onset of cell death in the attached cells was much slower than in the floating cells. Moreover, the cell death in the attached cells was either accelerated in a high-density culture (over ∼50% confluent), or inhibited in a low-density culture by NGF. While nucleosomal DNA fragmentation and poly (ADP-ribose) polymerase degradation was observed in both the floating and attached cells, the incidence of nuclear fragmentation and chromatin condensation was much lower in the attached cells than in the floating cells. The delayed onset of cell death in the attached cells was due to the signals that are generated from the extracellular matrix that is formed by PC12 cells, together with cell-to-cell interaction. The acceleration of cell death in the NGF-treated cells was anoikis, caused by the loss of the anchorage of the cell via the action of increased activities of matrix metalloproteinases (MMP2, MMP9). These results suggest that NGF has a different role in the cell death of PC12 cells that is induced by serum deprivation, depending on the cell-matrix, as well as the cell-cell interaction.