書誌事項
- タイトル別名
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- Search for toxic compounds from the mushroom Pleurocybella porrigens
抄録
The mushroom Pleurocybela porrigens (Angel's wings in English; Sugihiratake in Japanese) is widespread and common throughout temperate regions of the world. It has been eaten for a lng time all over the world. However, in autumn 2004 in Japan, fifty-five people got poisoned by eating this mushroom, and seventeen peoplel among them died of acute encephalopaty. There had been no report regarding toxocity of the fruiting bodies until the incident. Under these circumstances, we tried to isolate teh principle(s) of the disease. Purification of a glycoprotein showing lethal activity against mouse The mushroom was extracted with water and boiling water. After repeated chromatography of the water-soluble fractions, a glycoprotein was purified. The substance showed lethal toxocity toward mice at a dose of 24mg/kg (i.p.). Purification, characterization, and cDNA cloning of a lectin (PPL) PPL was purified from this mushroom. The results of SDS-PAGE gel filtration and MALDI-TOF-mass of PPL indicated that its molecular mass was 56kDa, and it was composed of four 14kDa subunits with no disulfide bonds. The complete amino acid sequence was determined by amino acid sequencing. The cDNA of PPL was cloned from RNA extracted from the mushroom. The open reading frame of the cDNA of the protein consisted of 411 bp encoding 137 amino acids. Intravenous (i.v.) (50mg/kg) or intraperitoneal (i.p.) (150mg/kg) administration of PPL to mice did not show any toxocity. However, i.v. (9mg/kg) administration of the protein to rats exhibited lethal toxocity. Purification of unusual amino acids showing cytotoxicity against mouse cerebrum glial cells Six amino acid derivatives (1-6) including three novel ones (1-3) were isolated from the mushroom. These compounds were cytotoxic to mouse glial cells. The structural novelty and analogy of the amino acids is such that each acid has the β-hydroxyvaline unit adducted to endogenous molecules, which inspired us to conclude the occurrence of an aziridine-amino acid (7) as the common precursor of the six compounds. We synthesized this compound and proved its occurrence in this mushroom. Compound 7 showed toxocity against rat CG4-16 oligodendrocyte cells; 7 significantly reduced the cell viability at concentrations up to 10μg/ml (87μM). Mechanism of the acute encephalopathy We found that a mixture of the letnal glycoprotein and PPL showed protease activity and disrupted the blood-brain barrier (BBB) in mice. We speculated that compound 7 or its derivatives caused demyelinating symptom after disruption of BBB. Verfication of the hypothesis is now on progress.
収録刊行物
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- 天然有機化合物討論会講演要旨集
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天然有機化合物討論会講演要旨集 52 (0), 655-660, 2010
天然有機化合物討論会実行委員会
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詳細情報 詳細情報について
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- CRID
- 1390001206080335360
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- NII論文ID
- 110009757834
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- ISSN
- 24331856
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- 本文言語コード
- ja
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- データソース種別
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- JaLC
- CiNii Articles
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- 抄録ライセンスフラグ
- 使用不可