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Neuronal Death and Neuroprotection

開催日 2014/9/11
時間 17:00 - 18:00
会場 Room I(311+312)
Chairperson(s) 木村 英雄 / Hideo Kimura ((独)国立精神・神経医療研究センター 神経研究所 神経薬理研究部 / Department of Molecular Pharmacology, National Institute of Neuroscience, NCNP, Japan)
小笠原 裕樹 / Yuki Ogasawara (明治薬科大学 分析化学教室 / Department of Analytical Biochemistry, Meiji Pharmaceutical University, Japan)

Prosurvival signals including Ca2+ regulation mediated by PDGF protect neurons from oxidative stress

  • O1-I-5-3
  • 石井 陽子 / Yoko Ishii:1 鄭 蓮順 / Lian-Shun Zheng:1,3 趙 慶利 / Qing-Li Zhao:2 近藤 隆 / Takashi Kondo:2 笹原 正清 / Masakiyo Sasahara:1 
  • 1:富山大院・医・病態病理学 / Dept Pathology, Univ of Toyama, Toyama, Japan 2:富山大院・医・放射線基礎医学 / Dept Radiological Sciences, Univ of Toyama, Toyama, Japan  3:浙江大・医・解剖細胞学 / Institute of Anatomy and Cell Biology, Univ of Zhejiang, Zhejiang, China 

Oxidative stress is crucially involved in the pathogenesis of neurological diseases such as stroke and degenerative diseases. The neuroprotective effects of platelet-derived growth factor (PDGF) and the major signaling pathways involved in these were examined using primary cultured mouse cortical neurons subjected to oxidative stress. PDGF-BB highly activated Akt, ERK, JNK and p38 in neurons. PDGF-AA activated these molecules at lesser extent than PDGF-BB. In particular, PDGF-AA induced activation of Akt was at very low level. The pretreatment with PDGF enhanced the survival of the neurons subjected to H2O2-induced oxidative stress, in which, both apoptotic and non-apoptotic cell death were improved. The prosurvival effect of PDGF-AA was less than that of PDGF-BB. The neuroprotective effect of PDGF-BB was antagonized by the inhibitors of PI3-K, MEK, JNK and p38, respectively. Alternatively, Ca2+ overload has been shown to mediate the neurotoxic effects of oxidative stress and excitotoxicity, and calpain is one of the downstream mediators of Ca2+ overload. The pretreatment with PDGF significantly suppressed the dose dependent Ca2+-overload after H2O2 in neuron, in which, the suppressive effects of PDGF-BB were more potent than those of PDGF-AA. Furthermore, the dose dependent calpain activation after H2O2 in neuron was completely suppressed by the pretreatment with PDGF-BB. Neuroprotective effects of PDGF were mediated by different signaling pathways. It was suggested that PDGF-BB might be a potential therapeutic target of neurological diseases.

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