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

Hdl Handle:
http://hdl.handle.net/10675.2/48
Title:
Mitochondrial BNIP3 upregulation precedes endonuclease G translocation in hippocampal neuronal death following oxygen-glucose deprivation.
Authors:
Zhao, Shen-Ting; Chen, Ming; Li, Shu-Ji; Zhang, Ming-Hai; Li, Bo-Xing; Das, Manas; Bean, Jonathan C; Kong, Ji-Ming; Zhu, Xin-Hong; Gao, Tian-Ming
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.
Citation:
BMC Neurosci. 2009 Sep 8; 10:113
Issue Date:
23-Sep-2009
URI:
http://hdl.handle.net/10675.2/48
DOI:
10.1186/1471-2202-10-113
PubMed ID:
19737385
PubMed Central ID:
PMC2749049
Type:
Journal Article; Research Support, Non-U.S. Gov't
ISSN:
1471-2202
Appears in Collections:
Institute of Molecular Medicine and Genetics: Faculty Research and Presentations

Full metadata record

DC FieldValue Language
dc.contributor.authorZhao, Shen-Tingen_US
dc.contributor.authorChen, Mingen_US
dc.contributor.authorLi, Shu-Jien_US
dc.contributor.authorZhang, Ming-Haien_US
dc.contributor.authorLi, Bo-Xingen_US
dc.contributor.authorDas, Manasen_US
dc.contributor.authorBean, Jonathan Cen_US
dc.contributor.authorKong, Ji-Mingen_US
dc.contributor.authorZhu, Xin-Hongen_US
dc.contributor.authorGao, Tian-Mingen_US
dc.date.accessioned2010-09-24T21:26:46Z-
dc.date.available2010-09-24T21:26:46Z-
dc.date.issued2009-09-23en_US
dc.identifier.citationBMC Neurosci. 2009 Sep 8; 10:113en_US
dc.identifier.issn1471-2202en_US
dc.identifier.pmid19737385en_US
dc.identifier.doi10.1186/1471-2202-10-113en_US
dc.identifier.urihttp://hdl.handle.net/10675.2/48-
dc.description.abstractBACKGROUND: 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.en_US
dc.rightsThe 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.meshAnalysis of Varianceen_US
dc.subject.meshAnimalsen_US
dc.subject.meshAnimals, Newbornen_US
dc.subject.meshApoptosis / genetics / physiologyen_US
dc.subject.meshBlotting, Westernen_US
dc.subject.meshCell Hypoxiaen_US
dc.subject.meshCells, Cultureden_US
dc.subject.meshEndodeoxyribonucleases / metabolism / physiologyen_US
dc.subject.meshGlucose / deficiencyen_US
dc.subject.meshHippocampus / cytology / metabolism / physiologyen_US
dc.subject.meshImmunohistochemistryen_US
dc.subject.meshMembrane Proteins / genetics / metabolism / physiologyen_US
dc.subject.meshMitochondria / genetics / metabolismen_US
dc.subject.meshMitochondrial Proteins / genetics / metabolism / physiologyen_US
dc.subject.meshNeurons / cytology / metabolism / physiologyen_US
dc.subject.meshProtein Transport / genetics / physiologyen_US
dc.subject.meshRNA Interferenceen_US
dc.subject.meshRatsen_US
dc.subject.meshRats, Sprague-Dawleyen_US
dc.subject.meshSubcellular Fractions / metabolism / physiologyen_US
dc.subject.meshTransfectionen_US
dc.subject.meshUp-Regulation / genetics / physiologyen_US
dc.titleMitochondrial BNIP3 upregulation precedes endonuclease G translocation in hippocampal neuronal death following oxygen-glucose deprivation.en_US
dc.typeJournal Articleen_US
dc.typeResearch Support, Non-U.S. Gov'ten_US
dc.identifier.pmcidPMC2749049en_US
dc.contributor.corporatenameInstitute of Molecular Medicine and Geneticsen_US
dc.contributor.corporatenameGraduate Program in Neuroscience-
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