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Cell Death Differ. 2004 Apr;11(4):403-15.

Ischemia-induced neuronal cell death is mediated by the endoplasmic reticulum stress pathway involving CHOP.

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1
Department of Molecular Genetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan. yanos@kaiju.medic.kumamoto-u.ac.jp

Abstract

Brain ischemia induces apoptosis in neuronal cells, but the mechanism is not well understood. 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.

PMID:
14752508
DOI:
10.1038/sj.cdd.4401365
[Indexed for MEDLINE]
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