Expression of the apoptosis-effector gene, Bax, is up-regulated in vulnerable hippocampal CA1 neurons following global ischemia.
The observation that delayed death of CA1 neurons after global ischemia is inhibited by protein synthesis inhibitors suggests that the delayed death of these neurons is an active process that requires new gene expression. Delayed death in CA1 has some of the characteristics of apoptotic death; however, candidate proapoptotic proteins have not been identified in the CA1 after ischemia. We studied the expression of Bax protein and mRNA, a member of the bcl-2 family that is an effector of apoptotic cell death, after global ischemia in the four-vessel global ischemia model in the rat and compared these results with the expression of the antiapoptotic gene bcl-2. Bax mRNA and protein are both expressed in CA1 before delayed death, whereas bcl-2 protein is not expressed. Bcl-2 protein expression, but not that of Bax, is increased in CA3, a region that is ischemic but less susceptible to ischemic injury. In the dentate gyrus, both Bax and bcl-2 proteins are expressed. The selective expression of Bax in Ca1 supports the hypothesis that Bax could contribute to delayed neuronal death in these vulnerable neurons by an independent mechanism or by forming heterodimers with gene family members other than bcl-2.
Chen
J
J
Department of Neurology, University of Pittsburgh, Pennsylvania 15261, USA.
Zhu
R L
RL
Nakayama
M
M
Kawaguchi
K
K
Jin
K
K
Stetler
R A
RA
Simon
R P
RP
Graham
S H
SH
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001483:Base Sequence; D001710:Biotin; D015152:Blotting, Northern; D015153:Blotting, Western; D004249:DNA Damage; D003856:Deoxyuracil Nucleotides; D019204:GTP-Binding Proteins / Q000235:genetics; D015870:Gene Expression / Q000502:physiology; D006624:Hippocampus / Q000166:cytology*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D008969:Molecular Sequence Data; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000235:genetics*; D013194:Staining and Labeling; D015854:Up-Regulation; D051028:bcl-2-Associated X Protein
C494828:Bax protein, rat; D003856:Deoxyuracil Nucleotides; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C027078:deoxyuridine triphosphate; D001710:Biotin; D019204:GTP-Binding Proteins