Bcl-Xshort is elevated following severe global ischemia in rat brains.
Hippocampal CA1 neurons are highly susceptible to short periods of transient global ischemia. We have previously reported in a rat model of transient forebrain global ischemia that activation and nuclear localization of NF-kB occurs in the CA1 neurons at 24 and 72 h post reperfusion. Events following NF-kB activation would ultimately determine whether damaged cells will undergo programmed cell death. We have selected bcl-x gene expression for study because there is increasing evidence that proteins encoded by the bcl-2 gene family (bcl-2, bcl-x, bax etc) play a role in the regulation of programmed cell death. We have observed that the bcl-x gene promoter contains a putative consensus sequence for NF-kB/CS4 responsive activation. We also can show that other members of the bcl-2 multigene family contain the NF-kB/CS4 sequence in their five prime regulatory regions. In this study, we show that NF-kB p50 and NF-kB p65 act in synergy to transactivate the bcl-x promoter in co-transfected 293 cells. We also report that following ischemia and NF-kB activation, bcl-x messenger RNA levels increase in the CA1 hippocampal region. As a result of this transcriptional increase, surprisingly, it is bcl-xs, the apoptotic form of bcl-x, that is elevated. These results suggest that activation of NF-kB can lead to increased expression of bcl-x as manifested by the increase in the short form of bcl-x.
Dixon
E P
EP
Lilly Research Laboratories, A Division of Eli Lilly and Company, Indianapolis, IN 46285, USA.
Stephenson
D T
DT
Clemens
J A
JA
Little
S P
SP
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D016384:Consensus Sequence; D005786:Gene Expression Regulation / Q000235:genetics; D017930:Genes, Reporter; D006624:Hippocampus / Q000098:blood supply / Q000166:cytology / Q000378:metabolism*; D002546:Ischemic Attack, Transient / Q000378:metabolism*; D016328:NF-kappa B / Q000032:analysis / Q000235:genetics; D010084:Oxidation-Reduction; D010957:Plasmids; D011401:Promoter Regions, Genetic / Q000235:genetics; D016548:Prosencephalon / Q000098:blood supply / Q000166:cytology / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000378:metabolism*; D017966:Pyramidal Cells / Q000166:cytology / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D051020:bcl-X Protein
C494813:Bcl2l1 protein, rat; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein