久米 利明

大西 正俊

泉 安彦

畝村 和宏

赤池 昭紀

香月 博志

高田 悠記

大西, 正俊

45377

香月, 博志

45378

9000261653307

畝村, 和宏

45379

泉, 安彦

45380

9000274377452

久米, 利明

45381

1000010303843

高田, 悠記

45382

9000001686859

赤池, 昭紀

45383

1000080135558

Fukuyama University Repository / 福山大学学術情報リポジトリ

− 66 −トロンビン誘発脳組織障害におけるHeme oxygenase-1 の関与大西正俊、香月博志＊、畝村和宏＊＊、泉　安彦＊＊、久米利明＊＊、髙鳥 (高田 )悠記＊＊＊、赤池昭紀＊＊Brain Research, 1347, 170-178 (2010)Heme oxygenase-1 contributes to pathology associated with thrombin-induced striatal and cortical injury in organotypic slice cultureMasatoshi Ohnishi, Hiroshi Katsuki*, Kazuhiro Unemura**, Yasuhiko Izumi**, Toshiaki Kume**, Yuki Takada-Takatori***, Akinori Akaike**ABSTRACT: A blood coagulation factor thrombin that leaks from ruptured vessels initiates brain tissue damage after intracerebral hemorrhage.  We have recently shown that mitogen-activated protein kinases (MAPKs) activated by thrombin exacerbate hemorrhagic brain injury via supporting survival of neuropathic microglia.  Here we investigated whether induction of heme oxygenase (HO)-1 is involved in these events.  Zinc protoporphyrin IX (ZnPP IX), a HO-1 inhibitor, attenuated thrombin-induced injury of cortical cells in a concentration-dependent manner (0.3 - 3 μM), and tended to inhibit shrinkage of the striatal tissue at 0.3 μM.  HO-1 expression was induced by thrombin in microglia and astrocytes in both the cortex and the striatum.  The increase of HO-1 protein was suppressed by a p38 MAPK inhibitor SB203580, and early activation of p38 MAPK after thrombin treatment was observed in neurons and microglia in the striatum.  Notably, concomitant application of a low concentration (0.3 μM) of ZnPP IX with thrombin induced apoptotic cell death in striatal microglia and signifi cantly decreased the number of activated microglia in the striatal region. On the other hand, a carbon monoxide releaser reversed the protective effect of ZnPP IX on thrombin-induced injury of cortical cells.  Overall, these results suggest that p38 MAPK-dependent induction of HO-1 supports survival of striatal microglia during thrombin insults. Thrombin-induced cortical injury also may be regulated by expression of HO-1 and resultant production of heme degradation products such as carbon monoxide.抄録　脳内出血時のニューロン障害性ミクログリアの生存維持における抗酸化酵素 heme oxygenase (HO)-1 の関与について解析を行った。培養脳組織切片において凝固系セリンプロテアーゼであるトロンビンは、p38 MAPK (mitogen-activated protein kinase) 活性化を介してグリア細胞に HO-1 を誘導した。HO-1 阻害薬である zinc (II) protoporphyrin (ZnPP) IX は、ミクログリアにアポトーシス性細胞死を惹起し、脳組織障害を減弱した。− 67 −* Department of Chemico-Pharmacological Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University　　熊本大学大学院生命科学研究部** Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University　　京都大学大学院薬学研究科*** Department of Pharmacology, Faculty of Pharmaceutical Sciences, Doshisha Women’s College　　同志社女子大学薬学部

Heme oxygenase-1 contributes to pathology associated with thrombin-induced striatal and cortical injury in organotypic slice culture

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トロンビン誘発脳組織障害におけるheme oxygenase-1 の関与(発表論文抄録(2009))

トロンビン誘発脳組織障害におけるheme oxygenase-1 の関与(発表論文抄録(2009))

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