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Volume 17, Number 4,
Issue of February 15, 1997
pp. 1397-1405
Copyright ©1997 Society for Neuroscience
p53 Expression Induces Apoptosis in Hippocampal Pyramidal Neuron
Cultures
Received Oct. 1, 1996; revised Nov. 27, 1996; accepted Dec. 4, 1996.
Joaquín Jordán1,
María F. Galindo1,
Jochen H. M. Prehn1,
Ralph
R. Weichselbaum2,
Michael Beckett2,
Ghanashyam D. Ghadge3,
Raymond P. Roos3,
Jeffrey M. Leiden4, and
Richard J. Miller1
Departments of 1 Pharmacological and Physiological
Sciences, 2 Radiation and Cell Oncology,
3 Neurology, and 4 Medicine, The University of
Chicago, Chicago, Illinois 60637
The tumor suppressor gene p53 has been implicated in the
induction of apoptosis in dividing cells. We now show that
overexpression of p53 using an adenoviral vector in cultured rat
hippocampal pyramidal neurons causes widespread neuronal death with
features typical of apoptosis. p53 overexpression did not induce p21,
bax, or mdm2 in neurons. X-irradiation of hippocampal neurons induced p53 immunoreactivity and cell death 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, overexpression of the
cyclin-dependent kinase inhibitor p21 did not. Treatment of neurons
with transforming growth factor- 1 protected them from x-irradiation.
These results are consistent with a role for p53 in nerve cell death
that is distinct from its actions relating to cell cycle arrest.
Key words:
adenovirus;
irradiation;
retinoblastoma;
tumor suppressor
genes;
overexpression;
p21;
transforming growth factor- 1
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