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Cerebrovascular Disease and Ischemia

開催日 2014/9/13
時間 11:00 - 12:00
会場 Poster / Exhibition(Event Hall B)

Phosphorylation enhances recombinant HSP27 neuroprotection against focal cerebral ischemia in mice

  • P3-327
  • 島田 佳明 / Yoshiaki Shimada:1 田中 亮太 / Ryota Tanaka:1 志村 秀樹 / Hideki Shimura:2,3 山城 一雄 / Kazuo Yamashiro:1 卜部 貴夫 / Takao Urabe:2 服部 信孝 / Nobutaka Hattori:1 
  • 1:順天堂大学医学部附属順天堂医院 脳神経内科 / Department of Neurology Juntendo University School of Medicine, Tokyo, Japan. 2:順天堂大学医学部附属浦安病院 脳神経内科 / Department of Neurology at Juntendo University Urayasu Hospital, Chiba, Japan. 3:順天堂大学大学院 環境医学研究所 / Institute for Environment and Gender Specific Medicine, Juntendo University School of Medicine Chiba, Japan  

Heat shock protein 27 (HSP27) exerts cytoprotection against many cellular insults including cerebral ischemia. We previously showed that intravenous injection of HSP27 purified from human lymphocytes (hHSP27) significantly reduced infarct volume following cerebral ischemia-reperfusion injury, while recombinant HSP27 (rHSP27) was less effective. Phosphorylation is important for HSP27 function, and hHSP27 was more highly phosphorylated than rHSP27. We hypothesized that MAPKAP kinase 2 in vitro-phosphorylated rHSP27 (prHSP27) might increase its brain protection. Mice underwent transient 1-h MCAO, and then received tail-vein injections of one of the following 1 h after reperfusion: hHSP27 as positive control, rHSP27, prHSP27, or bovine serum albumin (BSA) as control. We measured infarct volume, neurological deficits, neurological severity, physiological parameters, cell-death, oxidative stress, and inflammatory response. Compared with BSA controls (34.4±2.8mm3, n=5), infarct volume was reduced by 69% in the hHSP27 positive-control group (10.5±4.6mm3, P<0.001, n=5), 19% following rHSP27 (27.8±4.2mm3>, P<0.05, n=5), and 49% following prHSP27 (17.5±4.5mm3, P<0.001, n=9). Compared to the rHSP27 and BSA-treated groups, prHSP27 also reduced functional deficits, and significantly suppressed apoptosis, oxidative stress, and inflammatory responses. Here, we showed the superior neuroprotective effects of phosphorylated HSP27 by administering prHSP27. prHSP27 may be a useful therapeutic agent to protect against acute cerebral ischemic stroke.

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