Mitochondrial BNIP3 upregulation precedes endonuclease G translocation in hippocampal neuronal death following oxygen-glucose deprivation.
BACKGROUND
Caspase-independent apoptotic pathways are suggested as a mechanism for the delayed neuronal death following ischemic insult. However, the underlying signalling mechanisms are largely unknown. Recent studies imply the involvement of several mitochondrial proteins, including endonuclease G (EndoG) and Bcl-2/adenovirus E1B 19 kDa-interacting protein (BNIP3), in the pathway of non-neuronal cells.


RESULTS
In this report, using western blot analysis and immunocytochemistry, we found that EndoG upregulates and translocates from mitochondria to nucleus in a time-dependent manner in cultured hippocampal neurons following oxygen-glucose deprivation (OGD). Moreover, the translocation of EndoG occurs hours before the observable nuclear pyknosis. Importantly, the mitochondrial upregulation of BNIP3 precedes the translocation of EndoG. Forced expression of BNIP3 increases the nuclear translocation of EndoG and neuronal death while knockdown of BNIP3 decreases the OGD-induced nuclear translocation of EndoG and neuronal death.


CONCLUSIONS
These results suggest that BNIP3 and EndoG play important roles in hippocampal neuronal apoptosis following ischemia, and mitochondrial BNIP3 is a signal protein upstream of EndoG that can induce neuronal death.
Zhao
Shen-Ting
ST
Department of Neurobiology, Southern Medical University, Guangzhou, PR China. zhaoshenting2004@126.com
Chen
Ming
M
Li
Shu-Ji
SJ
Zhang
Ming-Hai
MH
Li
Bo-Xing
BX
Das
Manas
M
Bean
Jonathan C
JC
Kong
Ji-Ming
JM
Zhu
Xin-Hong
XH
Gao
Tian-Ming
TM
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D015153:Blotting, Western; D015687:Cell Hypoxia; D002478:Cells, Cultured; D004706:Endodeoxyribonucleases / Q000378:metabolism / Q000502:physiology*; D005947:Glucose / Q000172:deficiency; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D021381:Protein Transport / Q000235:genetics / Q000502:physiology; D034622:RNA Interference; D051381:Rats; D017207:Rats, Sprague-Dawley; D013347:Subcellular Fractions / Q000378:metabolism / Q000502:physiology; D014162:Transfection; D015854:Up-Regulation / Q000235:genetics / Q000502:physiology
C508686:BNip3 protein, mouse; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D004706:Endodeoxyribonucleases; C052391:endonuclease G; D005947:Glucose