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Titolo:
Expression of the endoplasmic reticulum molecular chaperone (ORP150) rescues hippocampal neurons from glutamate toxicity
Autore:
Kitao, Y; Ozawa, K; Miyazaki, M; Tamatani, M; Kobayashi, T; Yanagi, H; Okabe, M; Ikawa, M; Yamashima, T; Stern, DM; Hori, O; Ogawa, S;
Indirizzi:
Kanazawa Univ, Sch Med, Dept Neuroanat, Kanazawa, Ishikawa 9208640, Japan Kanazawa Univ Kanazawa Ishikawa Japan 9208640 wa, Ishikawa 9208640, Japan Japan Sci & Technol, Core Res Engn Sci & Technol, Kawaguchi, Japan Japan Sci & Technol Kawaguchi Japan ngn Sci & Technol, Kawaguchi, Japan Osaka Univ, Sch Med, Dept Anat & Neurosci, Suita, Osaka 565, Japan Osaka Univ Suita Osaka Japan 565 Anat & Neurosci, Suita, Osaka 565, Japan HSP Res Inst, Kyoto, Japan HSP Res Inst Kyoto JapanHSP Res Inst, Kyoto, Japan Osaka Univ, Genom Informat Serv Ctr, Suita, Osaka, Japan Osaka Univ SuitaOsaka Japan enom Informat Serv Ctr, Suita, Osaka, Japan Kanazawa Univ, Sch Med, Dept Neurosurg, Kanazawa, Ishikawa 9208640, Japan Kanazawa Univ Kanazawa Ishikawa Japan 9208640 wa, Ishikawa 9208640, Japan Columbia Univ, Coll Phys & Surg, Dept Surg, New York, NY USA Columbia Univ New York NY USA l Phys & Surg, Dept Surg, New York, NY USA Columbia Univ, Coll Phys & Surg, Dept Physiol, New York, NY USA Columbia Univ New York NY USA hys & Surg, Dept Physiol, New York, NY USA Columbia Univ, Coll Phys & Surg, Dept Cellular Biophys, New York, NY USA Columbia Univ New York NY USA g, Dept Cellular Biophys, New York, NY USA
Titolo Testata:
JOURNAL OF CLINICAL INVESTIGATION
fascicolo: 10, volume: 108, anno: 2001,
pagine: 1439 - 1450
SICI:
0021-9738(200111)108:10<1439:EOTERM>2.0.ZU;2-1
Fonte:
ISI
Lingua:
ENG
Soggetto:
OXYGEN-REGULATED PROTEIN; NF-KAPPA-B; OXIDATIVE STRESS; CELL-DEATH; EXCITOTOXIN HYPOTHESIS; CULTURED ASTROCYTES; CEREBRAL-ISCHEMIA; APOPTOSIS; RECEPTOR; NECROSIS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
36
Recensione:
Indirizzi per estratti:
Indirizzo: Kitao, Y Kanazawa Univ, Sch Med, Dept Neuroanat, 13-1 Takara Machi, Kanazawa, Ishikawa 9208640, Japan Kanazawa Univ 13-1 Takara Machi Kanazawa Ishikawa Japan 9208640 n
Citazione:
Y. Kitao et al., "Expression of the endoplasmic reticulum molecular chaperone (ORP150) rescues hippocampal neurons from glutamate toxicity", J CLIN INV, 108(10), 2001, pp. 1439-1450

Abstract

A series of events initiated by glutamate-receptor interaction perturbs cellular homeostasis resulting in elevation of intracellular free calcium andcell death. Cells subject to such environmental change express stress proteins, which contribute importantly to maintenance of metabolic homeostasis and viability. We show that an inducible chaperone present in endoplasmic reticulum (ER), the 150-kDa oxygen-regulated protein (ORP150), is expressed both in the human brain after seizure attack and in mouse hippocampus afterkainate administration. Using mice heterozygous for ORP150 deficiency, exposure to excitatory stimuli caused hippocampal neurons to display exaggerated elevation of cytosolic calcium accompanied by activation of mu -calpain and cathepsin B, as well as increased vulnerability to glutamate-induced cell death in vitro and decreased survival to kainate in vivo. In contrast, targeted neuronal overexpression of ORP150 suppressed each of these events and enhanced neuronal and animal survival in parallel with diminished seizure intensity. Studies using cultured hippocampal neurons showed that ORP150 regulates cytosolic free calcium and activation of proteolytic pathways causing cell death in neurons subject to excitatory stress. Our data underscore a possible role for ER stress in glutamate toxicity and pinpoint a key ERchaperone, ORP150, which contributes to the stress response critical for neuronal survival.

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Documento generato il 13/07/20 alle ore 10:10:52