{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1390001205658901632.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.14869/toxp.37.0.201.0"}},{"identifier":{"@type":"NAID","@value":"130007003805"}}],"dc:title":[{"@language":"en","@value":"The role of NAD (P) H: quinone oxidoreductase 1 on the detoxification of menadione"},{"@language":"ja","@value":"合成ビタミンKであるメナジオンの解毒代謝におけるNAD（P）H: quinone oxidoreductase 1の役割"}],"dc:language":"ja","description":[{"type":"abstract","notation":[{"@language":"ja","@value":"【目的】合成ビタミンKの一種であるメナジオン（MD）は，酸化ストレス研究における障害発生モデル化合物として広く用いられている。\nMDの毒性発現機序は，生体内においてMDが1電子還元を受け生成するセミキノンラジカルが酸化還元反応を繰り返す際に発生する活\n性酸素種によると考えられている。一方，MDの解毒代謝経路は，NAD（P）H: quinone oxidoreductase 1（NQO1）の2電子還元によ\nるメナジオール（MDOH）生成であると考えられている。しかしながら生成するMDOHは依然として活性酸素種を発生し毒性を示すこ\nとから，MDの解毒経路として疑問が持たれる。既に当研究室では，MDの解毒にはNQO1による還元反応のみならず，それに引き続\nく，UDP-グルクロン酸転移酵素（UGT）によるグルクロン酸抱合体生成が究極的な解毒経路であると示唆している。そこで本研究では，\nMDの解毒酵素として位置づけられているNQO1の役割について，UGTが発現していないことが知られているHEK293細胞を用いて再\n評価することを目的とした。<BR>\n【方法】HEK293細胞にNQO1あるいはNQO1およびUGTを同時発現させた細胞株を樹立した。これらの細胞にMDを添加し，24時間\n培養した。毒性の強弱は細胞生存率により評価した。<BR>\n【結果・考察】HEK293細胞に対するMDの毒性はwild-type HEK293細胞と比べ，NQO1を発現させた細胞では毒性が強く現れた。一方，\nNQO1とUGTを共に発現させた細胞では，wild-typeおよびNQO1のみの細胞と比べて毒性が軽減していた。以上の結果から，NQO1\nはMDの解毒ではなくむしろ毒性を増強することが明らかとなった。一方，UGTが存在することによって毒性が軽減されることから，\nメナジオンを解毒するには，NQO1に続き，UGTによる抱合反応が必要であることが明らかになった。"}],"abstractLicenseFlag":"disallow"}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1410290696027454212","@type":"Researcher","personIdentifier":[{"@type":"NRID","@value":"9000391998268"}],"foaf:name":[{"@language":"en","@value":"USAMI Mami"},{"@language":"ja","@value":"宇佐見 まみ"}],"jpcoar:affiliationName":[{"@language":"en","@value":"Department of Drug Metabolism and Molecular Toxicology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences"},{"@language":"ja","@value":"東京薬科大学薬学部薬物代謝安全性学教室"}]},{"@id":"https://cir.nii.ac.jp/crid/1420845751154931072","@type":"Researcher","personIdentifier":[{"@type":"KAKEN_RESEARCHERS","@value":"80307686"},{"@type":"NRID","@value":"1000080307686"},{"@type":"NRID","@value":"9000386308282"},{"@type":"NRID","@value":"9000391998269"},{"@type":"NRID","@value":"9000391911165"},{"@type":"NRID","@value":"9000391999742"},{"@type":"NRID","@value":"9000283498581"},{"@type":"NRID","@value":"9000003108387"},{"@type":"NRID","@value":"9000107314503"},{"@type":"NRID","@value":"9000283598639"},{"@type":"NRID","@value":"9000022207800"},{"@type":"NRID","@value":"9000005270092"},{"@type":"NRID","@value":"9000404853795"},{"@type":"NRID","@value":"9000252832015"},{"@type":"NRID","@value":"9000283498660"},{"@type":"NRID","@value":"9000402385949"},{"@type":"NRID","@value":"9000404539997"},{"@type":"NRID","@value":"9000257890142"},{"@type":"NRID","@value":"9000347193468"},{"@type":"NRID","@value":"9000258577191"},{"@type":"RESEARCHMAP","@value":"https://researchmap.jp/read0056718"}],"foaf:name":[{"@language":"en","@value":"NISHIYAMA Takahito"},{"@language":"ja","@value":"西山 貴仁"}],"jpcoar:affiliationName":[{"@language":"en","@value":"Department of Drug Metabolism and Molecular Toxicology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences"},{"@language":"ja","@value":"東京薬科大学薬学部薬物代謝安全性学教室"}]},{"@id":"https://cir.nii.ac.jp/crid/1410290696027454208","@type":"Researcher","personIdentifier":[{"@type":"NRID","@value":"9000391998270"}],"foaf:name":[{"@language":"en","@value":"OHNUMA Tomokazu"},{"@language":"ja","@value":"大沼 友和"}],"jpcoar:affiliationName":[{"@language":"en","@value":"Department of Drug Metabolism and Molecular Toxicology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences"},{"@language":"ja","@value":"東京薬科大学薬学部薬物代謝安全性学教室"}]},{"@id":"https://cir.nii.ac.jp/crid/1420845751158093696","@type":"Researcher","personIdentifier":[{"@type":"KAKEN_RESEARCHERS","@value":"10185564"},{"@type":"NRID","@value":"1000010185564"},{"@type":"NRID","@value":"9000003087857"},{"@type":"NRID","@value":"9000391911212"},{"@type":"NRID","@value":"9000386308287"},{"@type":"NRID","@value":"9000410151194"},{"@type":"NRID","@value":"9000392002430"},{"@type":"NRID","@value":"9000392002424"},{"@type":"NRID","@value":"9000391998271"},{"@type":"NRID","@value":"9000391911166"},{"@type":"NRID","@value":"9000391999744"},{"@type":"NRID","@value":"9000283498582"},{"@type":"NRID","@value":"9000391915009"},{"@type":"NRID","@value":"9000283797390"},{"@type":"NRID","@value":"9000005270091"},{"@type":"NRID","@value":"9000347046233"},{"@type":"NRID","@value":"9000391998248"},{"@type":"NRID","@value":"9000258576299"},{"@type":"NRID","@value":"9000107314500"},{"@type":"NRID","@value":"9000391911185"},{"@type":"NRID","@value":"9000022207801"},{"@type":"NRID","@value":"9000347140132"},{"@type":"NRID","@value":"9000347193168"},{"@type":"NRID","@value":"9000397802454"},{"@type":"NRID","@value":"9000258575257"},{"@type":"NRID","@value":"9000347140209"},{"@type":"NRID","@value":"9000254597139"},{"@type":"NRID","@value":"9000258573987"},{"@type":"NRID","@value":"9000386308270"},{"@type":"NRID","@value":"9000252832014"},{"@type":"NRID","@value":"9000283498668"},{"@type":"NRID","@value":"9000347140248"},{"@type":"NRID","@value":"9000258572646"},{"@type":"NRID","@value":"9000283794848"},{"@type":"NRID","@value":"9000392002463"},{"@type":"NRID","@value":"9000257890139"},{"@type":"NRID","@value":"9000415195914"},{"@type":"NRID","@value":"9000252860148"},{"@type":"NRID","@value":"9000252831341"},{"@type":"NRID","@value":"9000258572652"},{"@type":"NRID","@value":"9000258573195"},{"@type":"NRID","@value":"9000391915013"},{"@type":"NRID","@value":"9000253265290"},{"@type":"NRID","@value":"9000283797750"},{"@type":"NRID","@value":"9000347193472"},{"@type":"NRID","@value":"9000258712987"},{"@type":"NRID","@value":"9000392740772"},{"@type":"NRID","@value":"9000392746770"},{"@type":"RESEARCHMAP","@value":"https://researchmap.jp/read0027239"}],"foaf:name":[{"@language":"en","@value":"OGURA Kenichiro"},{"@language":"ja","@value":"小倉 健一郎"}],"jpcoar:affiliationName":[{"@language":"ja","@value":"東京薬科大学薬学部薬物代謝安全性学教室"},{"@language":"en","@value":"Department of Drug Metabolism and Molecular Toxicology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences"}]},{"@id":"https://cir.nii.ac.jp/crid/1410290696027454210","@type":"Researcher","personIdentifier":[{"@type":"NRID","@value":"9000391998272"}],"foaf:name":[{"@language":"en","@value":"HIRATSUKA Akira"},{"@language":"ja","@value":"平塚 明"}],"jpcoar:affiliationName":[{"@language":"en","@value":"Department of Drug Metabolism and Molecular Toxicology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences"},{"@language":"ja","@value":"東京薬科大学薬学部薬物代謝安全性学教室"}]}],"publication":{"prism:publicationName":[{"@language":"en","@value":"Annual Meeting of the Japanese Society of Toxicology"},{"@language":"ja","@value":"日本トキシコロジー学会学術年会"},{"@language":"en","@value":"Annual Meeting of the Japanese Society of Toxicology"},{"@language":"ja","@value":"日本トキシコロジー学会学術年会"}],"dc:publisher":[{"@language":"en","@value":"The Japanese Society of Toxicology"},{"@language":"ja","@value":"日本毒性学会"}],"prism:publicationDate":"2010","prism:volume":"37","prism:number":"0","prism:startingPage":"201","prism:endingPage":"201"},"availableAt":"2010","foaf:topic":[{"@id":"https://cir.nii.ac.jp/all?q=menadione","dc:title":"menadione"},{"@id":"https://cir.nii.ac.jp/all?q=NAD(P)H:quinone%20oxidoreductase%201","dc:title":"NAD(P)H:quinone oxidoreductase 1"},{"@id":"https://cir.nii.ac.jp/all?q=%E3%83%A1%E3%83%8A%E3%82%B8%E3%82%AA%E3%83%B3","dc:title":"メナジオン"},{"@id":"https://cir.nii.ac.jp/all?q=NAD(P)H:quinone%20oxidoreductase%201","dc:title":"NAD(P)H:quinone oxidoreductase 1"}],"dataSourceIdentifier":[{"@type":"JALC","@value":"oai:japanlinkcenter.org:1003280011"},{"@type":"CIA","@value":"130007003805"}]}