The proapoptotic member of the Bcl-2 family Bcl-2 / E1B-19K-interacting protein 3 is a mediator of caspase-independent neuronal death in excitotoxicity.
Caspase-independent neuronal death has been shown to occur in neuroexcitotoxicity. Here, we tested the hypothesis that the gene encoding Bcl-2/E1B-19K-interacting protein 3 (BNIP3) mediates caspase-independent neuronal death in excitotoxicity. BNIP3 was not detectable in neurons under normal condition. BNIP3 expression was increased dramatically in neurons in both in vivo and in vitro models of excitotoxicity. Expression of full-length BNIP3 in primary hippocampal neurons induced atypical cell death that required protein synthesis but was largely independent of caspase activities. Inhibition of BNIP3 expression by RNA interference protected against glutamate-induced neuronal cell death. Thus, BNIP3 activation and expression appears to be both necessary and sufficient for neuronal apoptosis in excitotoxicity. These results suggest that BNIP3 may be a new target for neuronal rescue strategies.
Department of Human Anatomy and Cell Science, University of Manitoba, Winnipeg, Manitoba, Canada.
Zhengfeng
Z
Zhang
Ruoyang
R
Shi
Jiequn
J
Weng
Xingshun
X
Xu
Xin-Min
XM
Li
Tian-ming
TM
Gao
Jiming
J
Kong
D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism*; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D024101:Mitochondrial Proteins; D009474:Neurons / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction
C505650:BNIP3 protein, rat; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D011518:Proto-Oncogene Proteins; D020169:Caspases