Mitochondrial BNIP3 upregulation precedes endonuclease G translocation in hippocampal neuronal death following oxygen-glucose deprivation.
dc.contributor.author | Zhao, Shen-Ting | |
dc.contributor.author | Chen, Ming | |
dc.contributor.author | Li, Shu-Ji | |
dc.contributor.author | Zhang, Ming-Hai | |
dc.contributor.author | Li, Bo-Xing | |
dc.contributor.author | Das, Manas | |
dc.contributor.author | Bean, Jonathan C | |
dc.contributor.author | Kong, Ji-Ming | |
dc.contributor.author | Zhu, Xin-Hong | |
dc.contributor.author | Gao, Tian-Ming | |
dc.date.accessioned | 2010-09-24T21:26:46Z | |
dc.date.available | 2010-09-24T21:26:46Z | |
dc.date.issued | 2009-09-23 | en_US |
dc.identifier.citation | BMC Neurosci. 2009 Sep 8; 10:113 | en_US |
dc.identifier.issn | 1471-2202 | en_US |
dc.identifier.pmid | 19737385 | en_US |
dc.identifier.doi | 10.1186/1471-2202-10-113 | en_US |
dc.identifier.uri | http://hdl.handle.net/10675.2/48 | |
dc.description.abstract | 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. CONCLUSION: 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. | |
dc.rights | The PMC Open Access Subset is a relatively small part of the total collection of articles in PMC. Articles in the PMC Open Access Subset are still protected by copyright, but are made available under a Creative Commons or similar license that generally allows more liberal redistribution and reuse than a traditional copyrighted work. Please refer to the license statement in each article for specific terms of use. The license terms are not identical for all articles in this subset. | en_US |
dc.subject.mesh | Analysis of Variance | en_US |
dc.subject.mesh | Animals | en_US |
dc.subject.mesh | Animals, Newborn | en_US |
dc.subject.mesh | Apoptosis / genetics / physiology | en_US |
dc.subject.mesh | Blotting, Western | en_US |
dc.subject.mesh | Cell Hypoxia | en_US |
dc.subject.mesh | Cells, Cultured | en_US |
dc.subject.mesh | Endodeoxyribonucleases / metabolism / physiology | en_US |
dc.subject.mesh | Glucose / deficiency | en_US |
dc.subject.mesh | Hippocampus / cytology / metabolism / physiology | en_US |
dc.subject.mesh | Immunohistochemistry | en_US |
dc.subject.mesh | Membrane Proteins / genetics / metabolism / physiology | en_US |
dc.subject.mesh | Mitochondria / genetics / metabolism | en_US |
dc.subject.mesh | Mitochondrial Proteins / genetics / metabolism / physiology | en_US |
dc.subject.mesh | Neurons / cytology / metabolism / physiology | en_US |
dc.subject.mesh | Protein Transport / genetics / physiology | en_US |
dc.subject.mesh | RNA Interference | en_US |
dc.subject.mesh | Rats | en_US |
dc.subject.mesh | Rats, Sprague-Dawley | en_US |
dc.subject.mesh | Subcellular Fractions / metabolism / physiology | en_US |
dc.subject.mesh | Transfection | en_US |
dc.subject.mesh | Up-Regulation / genetics / physiology | en_US |
dc.title | Mitochondrial BNIP3 upregulation precedes endonuclease G translocation in hippocampal neuronal death following oxygen-glucose deprivation. | en_US |
dc.type | Journal Article | en_US |
dc.type | Research Support, Non-U.S. Gov't | en_US |
dc.identifier.pmcid | PMC2749049 | en_US |
dc.contributor.corporatename | Institute of Molecular Medicine and Genetics | en_US |
dc.contributor.corporatename | Graduate Program in Neuroscience | |
refterms.dateFOA | 2019-04-09T21:00:17Z | |
html.description.abstract | 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. CONCLUSION: 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. |