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ORP150 protects against hypoxia/ischemia-induced neuronal death

Nature Medicine volume 7, pages 317–323 (2001)Cite this article

Abstract

Oxygen-regulated protein 150 kD (ORP150) is a novel endoplasmic-reticulum–associated chaperone induced by hypoxia/ischemia. Although ORP150 was sparingly upregulated in neurons from human brain undergoing ischemic stress, there was robust induction in astrocytes. Cultured neurons overexpressing ORP150 were resistant to hypoxemic stress, whereas astrocytes with inhibited ORP150 expression were more vulnerable. Mice with targeted neuronal overexpression of ORP150 had smaller strokes compared with controls. Neurons with increased ORP150 demonstrated suppressed caspase-3–like activity and enhanced brain-derived neurotrophic factor (BDNF) under hypoxia signaling. These data indicate that ORP150 is an integral participant in ischemic cytoprotective pathways.

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Figure 1: Expression of ORP150 in ischemic brain from patients with cerebral infarction.
Figure 2: Expression of ORP150 and cell death under hypoxia in cultured neurons and astrocytes.
Figure 3: Expression of ORP150 rescues cells from hypoxia-induced cytotoxicity.
Figure 4: Overexpression of ORP150 has no effect on neuronal death induced by SNP, hydrogen peroxide or staurosporine (□, control; ▪, AxORP150S; ░, AxLacZ).
Figure 5: Neuroprotective properties of ORP150 in transgenic mice.
Figure 6: ORP150 modulates secretion of BDNF.

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Acknowledgements

We thank I. Saito for providing AxCANLZ and Y. Hara for technical assistance. This work was supported by Inamori Foundation and CREST of Japan Science and Technology.

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Authors and Affiliations

  1. Department of Anatomy and Neuroscience, Graduate School of Medicine, Osaka University, Osaka, Japan

    Michio Tamatani, Atsushi Yamaguchi, Noriaki Mitsuda, Manabu Taniguchi, Yong Ho Che & Masaya Tohyama

  2. Fifth Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan

    Tomohiro Matsuyama & Hiroyuki Nishimura

  3. Department of Pathology, National Center for Cardiac Disease and Circulation Research, Osaka, Japan

    Yoshitane Tsukamoto

  4. Department of Neuroanatomy, Kanazawa University Medical School, Kanazawa, Japan

    Kentaro Ozawa, Osamu Hori & Satoshi Ogawa

  5. HSP Research Institute, Kyoto Research Park, Kyoto, Japan

    Atsuko Yamashita & Masaru Okabe

  6. Genome Information Research Center, Osaka University, Osaka

    Hideki Yanagi

  7. CREST, JST (Japan Science and Technology), College of Physicians and Surgeons, Columbia University, New York, New York, USA

    Michio Tamatani, Tomohiro Matsuyama, Atsushi Yamaguchi, Noriaki Mitsuda, Manabu Taniguchi, Yong Ho Che, Kentaro Ozawa, Osamu Hori, Satoshi Ogawa & Masaya Tohyama

  8. Department of Physiology and Cellular Biophysics, College of Physicians and Surgeons, Columbia University, New York, New York, USA

    David M. Stern

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Correspondence to Michio Tamatani.

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Tamatani, M., Matsuyama, T., Yamaguchi, A. et al. ORP150 protects against hypoxia/ischemia-induced neuronal death. Nat Med 7, 317–323 (2001). https://doi.org/10.1038/85463

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