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Journal of Neuroscience, Vol 15, 6364-6376, Copyright © 1995 by Society for Neuroscience
Upregulation of bax protein levels in neurons following cerebral ischemia
S Krajewski, JK Mai, M Krajewska, M Sikorska, MJ Mossakowski and JC Reed
La Jolla Cancer Research Foundation, Oncogene and Tumor Suppressor Gene Program, California 92037, USA.
The patterns of expression of the bcl-2, bax, and bci-X genes were examined
immunohistochemically in neurons of the adult rat brain before and after 10
min of global ischemia induced by transient cardiac arrest. High levels of
the cell death promoting protein Bax and concomitant low levels of the
apoptosis-blocking protein Bcl-2 were found in some populations of neurons
that are particularly sensitive to cell death induced by transient global
ischemia, such as the CA1 sector of the hippocampus and the Purkinje cells
of the cerebellum. Moreover, within 0.5 to 3 hr after an ischemic episode,
immunostaining for Bax was markedly increased within neurons with
morphological features of degeneration in many regions of the brain. Use of
a two-color staining method for simultaneous analysis of Bax protein and in
situ detection of DNA-strand breaks revealed high levels of Bax
immunoreactivity in many neurons undergoing apoptosis. Postischemic
elevations in Bax protein levels in the hippocampus, cortex, and cerebellum
were also demonstrated by immunoblotting. At early times after transient
ischemia, regulation of Bcl-2 and Bcl-x protein levels varied among
neuronal subpopulations, but from 3 hr on, those neurons with morphological
evidence of degeneration uniformly contained reduced levels of Bci-2 and
particularly Bci-X immunoreactivity. The findings suggest that differential
expression of some members of the bcl-2 gene family may play an important
role in determining the relative sensitivity of neuronal subpopulations to
ischemia and that postischemic alterations in the expression of bax, bcl-2,
and bcl-x may contribute to the delayed neuronal cell death that occurs
during the repurfusion phase after a transient ischemic episode.
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