P53 EXPRESSION INDUCES APOPTOSIS IN HIPPOCAMPAL PYRAMIDAL NEURON CULTURES

The tumor suppressor gene p53 has been implicated in the induction of apoptosis in dividing cells. We now show that overexpression of p53 us ing an adenoviral vector in cultured rat hippocampal pyramidal neurons causes widespread neuronal death with features typical of apoptosis. p53 overexpression did not induce p21, bar, or mdm2 in neurons. X-irra diation of hippocampal neurons induced p53 immunoreactivity and cell d eath associated with features typical of apoptosis. Overexpression of a constitutively active nonphosphorylatable form of the retinoblastoma gene product blocked x-irradiation-induced neuronal death. However, o verexpression of the cyclin-dependent kinase inhibitor p21 did not. Tr eatment of neurons with transforming growth factor-beta 1 protected th em from x-irradiation. These results are consistent with a role for p5 3 in nerve cell death that is distinct from its actions relating to ce ll cycle arrest.