Regucalcin confers resistance to amyloid‐β toxicity in neuronally differentiated <scp>PC</scp>12 cells

  • Tomiyasu Murata
    Laboratory of Analytical Neurobiology Faculty of Pharmacy Meijo University Nagoya Japan
  • Masayoshi Yamaguchi
    Department of Pathology and Laboratory Medicine David Geffen School of Medicine University of California, Los Angeles (UCLA) CA USA
  • Susumu Kohno
    Division of Oncology and Molecular Biology Cancer Research Institute Kanazawa University Ishikawa Japan
  • Chiaki Takahashi
    Division of Oncology and Molecular Biology Cancer Research Institute Kanazawa University Ishikawa Japan
  • Mitsumi Kakimoto
    Laboratory of Analytical Neurobiology Faculty of Pharmacy Meijo University Nagoya Japan
  • Yukiko Sugimura
    Laboratory of Analytical Neurobiology Faculty of Pharmacy Meijo University Nagoya Japan
  • Mako Kamihara
    Laboratory of Analytical Neurobiology Faculty of Pharmacy Meijo University Nagoya Japan
  • Kiyomi Hikita
    Laboratory of Analytical Neurobiology Faculty of Pharmacy Meijo University Nagoya Japan
  • Norio Kaneda
    Laboratory of Analytical Neurobiology Faculty of Pharmacy Meijo University Nagoya Japan

書誌事項

公開日
2018-01-20
資源種別
journal article
権利情報
  • http://creativecommons.org/licenses/by/4.0/
DOI
  • 10.1002/2211-5463.12374
公開者
Wiley

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説明

<jats:p>Amyloid‐β (Aβ), a primary component of amyloid plaques, has been widely associated with the pathogenesis of Alzheimer's disease. The Ca<jats:sup>2+</jats:sup>‐binding protein regucalcin (RGN) plays multiple roles in maintaining cell functions by regulating intracellular calcium homeostasis, various signaling pathways, and gene expression systems. Here, we investigated the functional role of RGN against Aβ‐induced cytotoxicity in neuronally differentiated <jats:styled-content style="fixed-case">PC</jats:styled-content>12 cells. Overexpression of RGN reduced Aβ‐induced apoptosis by reducing mitochondrial dysfunction and caspase activation. It also attenuated Aβ‐induced reactive oxygen species production and oxidative damage and decreased Aβ‐induced nitric oxide (NO) overproduction, upregulation of inducible NO synthase by nuclear factor‐κB, and nitrosative damage. Interestingly, the genetic disruption of RGN increased the susceptibility of neuronally differentiated <jats:styled-content style="fixed-case">PC</jats:styled-content>12 cells to Aβ toxicity. Thus, RGN possesses antioxidant activity against Aβ‐induced oxidative and nitrosative stress and may play protective roles against Aβ‐induced neurotoxicity in Alzheimer's disease.</jats:p>

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