Open Access Research article

Mitochondrial BNIP3 upregulation precedes endonuclease G translocation in hippocampal neuronal death following oxygen-glucose deprivation

Shen-Ting Zhao1, Ming Chen1, Shu-Ji Li1, Ming-Hai Zhang1, Bo-Xing Li1, Manas Das1, Jonathan C Bean3, Ji-Ming Kong12, Xin-Hong Zhu1* and Tian-Ming Gao1*

Author Affiliations

1 Department of Neurobiology, Southern Medical University, Guangzhou, PR China

2 Department of Human Anatomy and Cell Science, University of Manitoba Faculty of Medicine, Winnipeg, Man., Canada

3 Department of Neuroscience, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, Georgia, USA

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BMC Neuroscience 2009, 10:113  doi:10.1186/1471-2202-10-113

Published: 8 September 2009



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.


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.


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.