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演題詳細

Oral

神経細胞死・神経変性
Neuronal Death and Neurodegeneration

開催日 2014/9/11
時間 18:00 - 19:00
会場 Room I(311+312)
Chairperson(s) 岡澤 均 / Hitoshi Okazawa (東京医科歯科大学 / Tokyo Medical and Dental University, Japan)
渡部 和彦 / Kazuhiko Watabe (東京都医学総合研究所 神経変性病理 / ALS/Neuropathy Project, Tokyo Metropolitan Institute of Medical Science, Japan)

脳虚血マーカーである抗熱ショックタンパク質70 kDa抗体はH2O2を介して神経細胞死を惹起する
An anti-HSP70 antibody, a marker of brain ischemia, induced neuronal cell death via H2O2

  • O1-I-6-4
  • 矢上 達郎 / Tatsuro Yagami:1 山本 泰弘 / Yasuhiro Yamamoto:1 高馬 宏美 / Hiromi Koma:1 太田 栄亮 / Eisuke Ohta:1 
  • 1:姫路獨協大学 / Himeji Dokkyo University, Japan 

Ischemic stroke is connected with a significant elevation of 15-deoxy-Δ12,14-prostaglandin J2 (15d-PG J2), heat shock protein 70 (HSP70) and anti-HSP70 antibody levels. Although HSP70 protects neurons from apoptosis, it has not yet been clarified how 15d-PG J2 and the anti-HSP70 antibody are involved in stroke. To this end, we examined pathological roles of 15d-PG J2 and the anti-HSP70 antibody in stroke. HSP70 was colocalized with membrane targets for 15d-PG J2 at the surface of neuronal cell bodies. The anti-HSP70 antibody recognized a plasmalemmal HSP70 and induced cell death in the primary culture of rat cortical neurons. The anti-HSP70 antibody generated neurotoxic H2O2, but did not activate caspase-3. Catalase suppressed neurons from undergoing anti-HSP70 antibody-induced cell death and H2O2. The post-treatment of neurons with catalase after the application of the anti-HSP70 antibody exhibited the neuroprotective effect as well as the co-treatment. 15d-PGJ2 enhanced the neurotoxicity of the anti-HSP70 antibody. An antagonist for peroxysome-proliferator activated receptor γ (PPAR γ), a nuclear 15d-PGJ2 receptor, did not suppress the neurotoxicity of 15d-PGJ2 and the anti-HSP70 antibody. The anti-HSP70 antibody caused neuronal cell death via H2O2. Catalase suppressed the neurotoxicity of the anti-HSP70 antibody, confirmed the therapeutic potential of antioxidants including catalase for stroke. 15d-PGJ2 augmented the anti-HSP70 antibody-induced neuronal cell death, suggested that 15d-PGJ2 and the anti-HSP70 antibody played pathological roles as neurotoxicants in stroke.

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