Jx. Qiu et al., Differential NF-kappa B regulation of bcl-x gene expression in hippocampusand basal forebrain in response to hypoxia, J NEUROSC R, 64(3), 2001, pp. 223-234
Cell death often occurs after hypoxic/ischemic injury to the central nervou
s system. Changes in levels of the anti-apoptotic Bcl-X-L protein may be a
determining factor in hypoxia-induced neuronal apoptosis. The transcription
factor NF-kappaB regulates bcl-x gene expression. In this study, we examin
ed the role of NF-kappaB in the regulation of bcl-x in hypoxia-induced cell
death. Rat hippocampus and basal forebrain tissues were collected at diffe
rent time points after hypoxia (7%O-2, 93% N-2 for 10 or 20 min). We found
that 1) hypoxia induced apoptosis in the hippocampus and basal forebrain; 2
) the NF-kappaB dimers c-Rel/p50 and p50/p50 bound to the bcl-x promoter NF
-kappaB sequence (CS4) in the hippocampus, but only p50/p50 bound to the CS
4 sequence in the basal forebrain and hypoxia-induced differential binding
patterns of c-Rel/p50 and p50/p50 correlated with the bcl-x expression patt
ern in the hippocampus; 3) the hypoxiainduced patterns of binding of c-Rel/
p50 to the bcl-x promoter CS4 sequence were different from those to the IgG
-kappaB enhancer sequence, whereas those of p50/p50 were similar to both se
quences; 4) nuclear protein levels of c-Rel, but not p50, correlated with t
he c-Rel/p50 DNA binding patterns to the bcl-x CS4 site; and 5) there were
differential responses to hypoxia among the different NF-kappaB protein sub
units, These results suggest that there is a tissue-specific regulation of
bcl-x gene expression by NF-kappaB in hypoxia-induced cell death in the hip
pocampus. The absence of these regulating features in the basal forebrain m
ay account for the early appearance of apoptosis in response to hypoxia as
compared with that in hippocampus, (C) 2001 Wiley-Liss, Inc.