1. ^*Department of Neuroanatomy, Kanazawa University Medical School, Kanazawa City, Ishikawa, Japan
2. ^†Division of Strokology, Department of Internal Medicine, Osaka University Graduate School of Medicine, Osaka, Japan
3. ^‡Core Research for Engineering, Science, and Technology (CREST), Japan Science and Technology, Kawaguchi, Japan
4. ^§Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya City, Hyogo, Japan

Correspondence: Kentaro Ozawa, Department of Neuroanatomy, Kanazawa University Medical School, 13–1, Takara-machi, Kanazawa City, Ishikawa, 920–8640, Japan; e-mail: ozawa@nanat.m.kanazawa-u.ac.jp

Received 7 January 2002; Revised 29 April 2002; Accepted 29 April 2002.

Abstract

ORP150—150-kd oxygen-regulated protein—is a novel stress protein localized in the endoplasmic reticulum (ER). To investigate the role of ORP150 in delayed neuronal cell death, the authors examined its expression in the gerbil brain after an ischemic insult. The expression of ORP150 antigen, as well as its transcripts, was observed in the CA1 region after the occlusion of the common carotid artery, and the preconditioning enhanced this expression. In cultured neurons, exposure either to hypoxia or to glutamate induced the expression of ORP150, and this effect was also observed by treating the culture with breferdin A or thapsigargin, indicating that both glutamate and hypoxia can cause stress in the ER (ER stress). Neurons became more vulnerable to these stresses following treatment with cycloheximide or after infection with an adenovirus carrying the ORP150-antisense structure. In contrast, the overexpression of ORP150 by an adenovirus suppressed neuronal cell death, and this was accompanied by the suppression of Ca²⁺ elevation and proteolytic activity induced by glutamate. Further, overexpression of ORP150 in CA1 neurons by an adenovirus carrying the ORP150-sense structure suppressed delayed neuronal cell death after ischemia. These data suggest a possible function of ORP150 as an intracellular apparatus that participates in a protective response in ischemic tolerance.