ORP150/HSP12A Regulates Purkinje Cell Survival

A Role for Endoplasmic Reticulum Stress in Cerebellar Development

Yasuko Kitao, Kouichi Hashimoto, Tomohiro Matsuyama, Hiroyuki Iso, Takeshi Tamatani, Osamu Hori, David Stern, Masanobu Kano, Kentaro Ozawa, Satoshi Ogawa

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

The endoplasmic reticulum (ER) stress response contributes to neuronal survival in ischemia and neurodegenerative processes. ORP150 (oxygen-regulated protein 150)/HSP12A (heat shock protein 12A), a novel stress protein located in the ER, was markedly induced in Purkinje cells maximally at 4 - 8 d after birth, a developmental period corresponding to their vulnerability to cell death. Both terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end-labeling analysis and immunostaining using anti-activated caspase-3 antibody revealed that transgenic mice with targeted neuronal overexpression of ORP150 (Tg ORP150) displayed diminished cell death in the Purkinje cell layer and increased numbers of Purkinje cells up to 40 d after birth (p < 0.01), compared with those observed in heterozygous ORP150/HSP12A-deficient (ORP150+/-) mice and wild-type littermates (ORP150+/+). Cultured Purkinje cells from Tg ORP150 mice displayed resistance to both hypoxia- and AMPA-induced stress. Behavioral analysis, using rotor rod tasks, indicated impairment of cerebellar function in Tg ORP150 animals, consistent with the concept that enhanced survival of Purkinje cells results in dysfunction. These data suggest that ER chaperones have a pivotal role in Purkinje cell survival and death and thus may highlight the importance of ER stress in neuronal development.

Original languageEnglish (US)
Pages (from-to)1486-1496
Number of pages11
JournalJournal of Neuroscience
Volume24
Issue number6
DOIs
StatePublished - Feb 11 2004

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Endoplasmic Reticulum Stress
Purkinje Cells
Cell Survival
Cell Death
Heat-Shock Proteins
Endoplasmic Reticulum
Parturition
Uridine Triphosphate
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
DNA Nucleotidylexotransferase
Caspase 3
Transgenic Mice
oxygen-regulated proteins
Cultured Cells
Ischemia
Antibodies

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

ORP150/HSP12A Regulates Purkinje Cell Survival : A Role for Endoplasmic Reticulum Stress in Cerebellar Development. / Kitao, Yasuko; Hashimoto, Kouichi; Matsuyama, Tomohiro; Iso, Hiroyuki; Tamatani, Takeshi; Hori, Osamu; Stern, David; Kano, Masanobu; Ozawa, Kentaro; Ogawa, Satoshi.

In: Journal of Neuroscience, Vol. 24, No. 6, 11.02.2004, p. 1486-1496.

Research output: Contribution to journalArticle

Kitao, Y, Hashimoto, K, Matsuyama, T, Iso, H, Tamatani, T, Hori, O, Stern, D, Kano, M, Ozawa, K & Ogawa, S 2004, 'ORP150/HSP12A Regulates Purkinje Cell Survival: A Role for Endoplasmic Reticulum Stress in Cerebellar Development', Journal of Neuroscience, vol. 24, no. 6, pp. 1486-1496. https://doi.org/10.1523/JNEUROSCI.4029-03.2004
Kitao, Yasuko ; Hashimoto, Kouichi ; Matsuyama, Tomohiro ; Iso, Hiroyuki ; Tamatani, Takeshi ; Hori, Osamu ; Stern, David ; Kano, Masanobu ; Ozawa, Kentaro ; Ogawa, Satoshi. / ORP150/HSP12A Regulates Purkinje Cell Survival : A Role for Endoplasmic Reticulum Stress in Cerebellar Development. In: Journal of Neuroscience. 2004 ; Vol. 24, No. 6. pp. 1486-1496.
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