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A molecular chaperone inducer protects neurons from ER stress.
Cell Death Differ. 2008 Feb; 15(2):364-75.CD

Abstract

The endoplasmic reticulum (ER) stress response is a defense system for dealing with the accumulation of unfolded proteins in the ER lumen. Recent reports have shown that ER stress is involved in the pathology of some neurodegenerative diseases and cerebral ischemia. In a screen for compounds that induce the ER-mediated chaperone BiP (immunoglobulin heavy-chain binding protein)/GRP78 (78 kDa glucose-regulated protein), we identified BiP inducer X (BIX). BIX preferentially induced BiP with slight inductions of GRP94 (94 kDa glucose-regulated protein), calreticulin, and C/EBP homologous protein. The induction of BiP mRNA by BIX was mediated by activation of ER stress response elements upstream of the BiP gene, through the ATF6 (activating transcription factor 6) pathway. Pretreatment of neuroblastoma cells with BIX reduced cell death induced by ER stress. Intracerebroventricular pretreatment with BIX reduced the area of infarction due to focal cerebral ischemia in mice. In the penumbra of BIX-treated mice, ER stress-induced apoptosis was suppressed, leading to a reduction in the number of apoptotic cells. Considering these results together, it appears that BIX induces BiP to prevent neuronal death by ER stress, suggesting that it may be a potential therapeutic agent for cerebral diseases caused by ER stress.

Authors+Show Affiliations

Psychiatry, Department of Integrated Medicine, Division of Internal Medicine, Osaka University Graduate School of Medicine, Suita, Japan. kudo@psy.med.osaka-u.ac.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18049481

Citation

Kudo, T, et al. "A Molecular Chaperone Inducer Protects Neurons From ER Stress." Cell Death and Differentiation, vol. 15, no. 2, 2008, pp. 364-75.
Kudo T, Kanemoto S, Hara H, et al. A molecular chaperone inducer protects neurons from ER stress. Cell Death Differ. 2008;15(2):364-75.
Kudo, T., Kanemoto, S., Hara, H., Morimoto, N., Morihara, T., Kimura, R., Tabira, T., Imaizumi, K., & Takeda, M. (2008). A molecular chaperone inducer protects neurons from ER stress. Cell Death and Differentiation, 15(2), 364-75.
Kudo T, et al. A Molecular Chaperone Inducer Protects Neurons From ER Stress. Cell Death Differ. 2008;15(2):364-75. PubMed PMID: 18049481.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A molecular chaperone inducer protects neurons from ER stress. AU - Kudo,T, AU - Kanemoto,S, AU - Hara,H, AU - Morimoto,N, AU - Morihara,T, AU - Kimura,R, AU - Tabira,T, AU - Imaizumi,K, AU - Takeda,M, Y1 - 2007/11/30/ PY - 2007/12/1/pubmed PY - 2008/4/4/medline PY - 2007/12/1/entrez SP - 364 EP - 75 JF - Cell death and differentiation JO - Cell Death Differ VL - 15 IS - 2 N2 - The endoplasmic reticulum (ER) stress response is a defense system for dealing with the accumulation of unfolded proteins in the ER lumen. Recent reports have shown that ER stress is involved in the pathology of some neurodegenerative diseases and cerebral ischemia. In a screen for compounds that induce the ER-mediated chaperone BiP (immunoglobulin heavy-chain binding protein)/GRP78 (78 kDa glucose-regulated protein), we identified BiP inducer X (BIX). BIX preferentially induced BiP with slight inductions of GRP94 (94 kDa glucose-regulated protein), calreticulin, and C/EBP homologous protein. The induction of BiP mRNA by BIX was mediated by activation of ER stress response elements upstream of the BiP gene, through the ATF6 (activating transcription factor 6) pathway. Pretreatment of neuroblastoma cells with BIX reduced cell death induced by ER stress. Intracerebroventricular pretreatment with BIX reduced the area of infarction due to focal cerebral ischemia in mice. In the penumbra of BIX-treated mice, ER stress-induced apoptosis was suppressed, leading to a reduction in the number of apoptotic cells. Considering these results together, it appears that BIX induces BiP to prevent neuronal death by ER stress, suggesting that it may be a potential therapeutic agent for cerebral diseases caused by ER stress. SN - 1350-9047 UR - https://www.unboundmedicine.com/medline/citation/18049481/A_molecular_chaperone_inducer_protects_neurons_from_ER_stress_ L2 - https://doi.org/10.1038/sj.cdd.4402276 DB - PRIME DP - Unbound Medicine ER -