2005 Fiscal Year Final Research Report Summary
Role of ER-stress on ischemic neuronal cell death
| Project/Area Number |
16591448
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Cerebral neurosurgery
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| Research Institution | Kumamoto University |
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Principal Investigator |
YANO Shigetoshi Kumamoto University, Neurosurgery, Instructor, 医学部附属病院, 助手 (60332871)
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| Co-Investigator(Kenkyū-buntansha) |
MORIOKA Motohiro Kumamoto Univ., Neurosurgery, Assistant Professor, 医学部附属病院, 講師 (20295140)
KAI Yutaka Kumamoto University, Neurosurgery, Instructor, 大学院・医学薬学研究部, 助手 (30322308)
MORI Masataka Kumamoto University, Morecular Genetics, Professor, 大学院・医学薬学研究部, 教授 (40009650)
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| Project Period (FY) |
2004 – 2005
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| Keywords | CHOP / ER stress / BiP / hypoxia / ischemia / apoptosis |
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| Research Abstract |
To investigate the roll of ER stress on neuronal cell death in cerebral ischemia, we focused on CHOP which is inducible ER-stress protein and known to induce apoptosis.
When wild-type mice were subjected to bilateral common carotid arteries occlusion (BCCAO) for 15 min, apoptosis-associated morphological changes and appearance of TUNEL-positive cells were observed in the striatum and in the hippocampus at 48 h after occlusion. RT-PCR analysis revealed that mRNAs for ER stress-associated proapoptotic factor CHOP and an ER chaperone BiP are markedly induced at 12 h after BCCAO. Immunohistochemical analysis showed that CHOP protein is induced in nuclei of damaged neurons at 24 h after occlusion. In contrast, ischemia-associated apoptotic loss of neurons was decreased in CHOP(-/-) mice. Primary hippocampal neurons from CHOP(-/-) mice were more resistant to hypoxia-reoxygenation-induced apoptosis than those from wild-type animals. These results indicate that ischemia-induced neuronal cell death is mediated by the ER stress pathway involving CHOP induction.
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