Differentiated Cells Are More Vulnerable to Apoptosis in PC12 Cells

Objectives: The aim of the present study was to investigate whether differentiated PC12 cells are more vulnerable to apoptosis than undifferentiated PC12 cells in response to staurosporine. Methods: Differentiation of PC12 cells was induced using NGF. Cell death in PC12 cells was measured using the MTT assay. Poly (ADP-ribose) polymerase (PARP) cleavage and expression of Bcl-xl were detected using Western blotting. Results: PC12 cells that have been induced to differentiate by NGF treatment undergo more rapid cell death compared with undifferentiated PC12 cells in response to staurosporine. In addition, staurosporine induced more rapid cleavage of PARP in differentiated PC12 cells, suggesting that caspases are activated more rapidly in differentiated cells. One of the most important regulators of caspase activity is Bcl-xl, which is known to prevent caspase-3 activation. We found that Bcl-xl was less expressed in differentiated PC12 cells. Furthermore, during the exposure of PC12 cells to staurosporine, total amount of Bcl-xl was found to decrease gradually, suggesting that the lower level of Bcl-xl expression in the differentiated PC12 cells may result in more rapid induction of apoptosis. This was strongly supported by the observation that the overexpression of Bcl-xl prevented the caspase-3 activation and apoptosis induced by staurosporine. Conclusions: Differentiated PC12 cells are more vulnerable to staurosporine-induced apoptosis than undifferentiated PC12 cells, probably due to the lower expression of Bcl-xl in the differentiated cells.