BNIP3 mediates pre-myelinating oligodendrocyte cell death in hypoxia and ischemia
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作者:
Li, Chengren
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Third Mil Med Univ, Fac Basic Med, Dept Histol & Embryol, Chongqing 400038, Peoples R China
Univ Manitoba, Fac Med, Dept Human Anat & Cell Sci, Winnipeg, MB R3E 0J9, CanadaThird Mil Med Univ, Fac Basic Med, Dept Histol & Embryol, Chongqing 400038, Peoples R China
Li, Chengren
[1
,2
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Guan, Teng
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Univ Manitoba, Fac Med, Dept Human Anat & Cell Sci, Winnipeg, MB R3E 0J9, CanadaThird Mil Med Univ, Fac Basic Med, Dept Histol & Embryol, Chongqing 400038, Peoples R China
Guan, Teng
[2
]
Chen, Xueping
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机构:
Univ Manitoba, Fac Med, Dept Human Anat & Cell Sci, Winnipeg, MB R3E 0J9, Canada
Sichuan Univ, West China Hosp, Dept Neurol, Chengdu 610064, Peoples R ChinaThird Mil Med Univ, Fac Basic Med, Dept Histol & Embryol, Chongqing 400038, Peoples R China
Chen, Xueping
[2
,3
]
Li, Wenyan
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Univ Manitoba, Fac Med, Dept Human Anat & Cell Sci, Winnipeg, MB R3E 0J9, CanadaThird Mil Med Univ, Fac Basic Med, Dept Histol & Embryol, Chongqing 400038, Peoples R China
Li, Wenyan
[2
]
Cai, Qiyan
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Third Mil Med Univ, Fac Basic Med, Dept Histol & Embryol, Chongqing 400038, Peoples R ChinaThird Mil Med Univ, Fac Basic Med, Dept Histol & Embryol, Chongqing 400038, Peoples R China
Cai, Qiyan
[1
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Niu, Jianqin
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Third Mil Med Univ, Fac Basic Med, Dept Histol & Embryol, Chongqing 400038, Peoples R ChinaThird Mil Med Univ, Fac Basic Med, Dept Histol & Embryol, Chongqing 400038, Peoples R China
Niu, Jianqin
[1
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Xiao, Lan
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Third Mil Med Univ, Fac Basic Med, Dept Histol & Embryol, Chongqing 400038, Peoples R ChinaThird Mil Med Univ, Fac Basic Med, Dept Histol & Embryol, Chongqing 400038, Peoples R China
Xiao, Lan
[1
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Kong, Jiming
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Univ Manitoba, Fac Med, Dept Human Anat & Cell Sci, Winnipeg, MB R3E 0J9, CanadaThird Mil Med Univ, Fac Basic Med, Dept Histol & Embryol, Chongqing 400038, Peoples R China
Kong, Jiming
[2
]
机构:
[1] Third Mil Med Univ, Fac Basic Med, Dept Histol & Embryol, Chongqing 400038, Peoples R China
[2] Univ Manitoba, Fac Med, Dept Human Anat & Cell Sci, Winnipeg, MB R3E 0J9, Canada
[3] Sichuan Univ, West China Hosp, Dept Neurol, Chengdu 610064, Peoples R China
Developing oligodendrocytes, collectively termed pre-myelinating oligodendrocytes' (preOLs), are vulnerable to hypoxic or ischemic insults. The underlying mechanism of this vulnerability remains unclear. Previously, we showed that Bcl-2/E1B-19K-interacting protein 3 (BNIP3), a proapoptotic member of the Bcl-2 family proteins, induced neuronal death in a caspase-independent manner in stroke. In this study, we investigated the role of BNIP3 in preOL cell death induced by hypoxia or ischemia. In primary oligodendrocyte progenitor cell (OPC) cultures exposed to oxygen-glucose deprivation, we found that BNIP3 was upregulated and levels of BNIP3 expression correlated with the death of OPCs. Up-regulation of BNIP3 was observed in preOLs in the white matter in a neonatal rat model of stroke. Knockout of BNIP3 significantly reduced death of preOLs in the middle cerebral artery occlusion model in mice. Our results demonstrate a role of BNIP3 in mediating preOLs cell death induced by hypoxia or ischemia, and suggest that BNIP3 may be a new target for protecting oligodendrocytes from death after stroke.
机构:
Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USAUniv Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USA