{"created":"2023-07-27T06:58:35.252577+00:00","id":57253,"links":{},"metadata":{"_buckets":{"deposit":"d063f70d-0e10-4b58-9947-f62aefb654e4"},"_deposit":{"created_by":18,"id":"57253","owners":[18],"pid":{"revision_id":0,"type":"depid","value":"57253"},"status":"published"},"_oai":{"id":"oai:kanazawa-u.repo.nii.ac.jp:00057253","sets":["2812:2813:2831"]},"author_link":["185"],"item_9_biblio_info_8":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2004-04-13","bibliographicIssueDateType":"Issued"},"bibliographicPageStart":"2p.","bibliographicVolumeNumber":"2000 – 2002","bibliographic_titles":[{"bibliographic_title":"平成14(2002)年度 科学研究費補助金 基盤研究(B) 研究成果報告書概要"},{"bibliographic_title":"2002 Fiscal Year Final Research Report Summary","bibliographic_titleLang":"en"}]}]},"item_9_creator_33":{"attribute_name":"著者別表示","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{}],"nameIdentifiers":[{},{},{}]}]},"item_9_description_21":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"リポキシゲナーゼ(Lipoxygenase)は,不飽和脂肪酸に酸素を添加する酵素であり,マルチジーンファミリーを形成している。炭素数20個のアラキドン酸への酸素添加の位置の違いによって,5-,8-,12-,15-リポキシゲナーゼがある。5-リポキシゲナーゼは炎症や免疫に関与するロイコトリエンを生合成し,12/15-リポキシゲナーゼは動脈硬化症などの炎症性疾患において注目されている。動脈硬化病巣においては,低比重リポタンパク質(LDL)の酸化,酸化LDLの受容体やスカベンジャー受容体が重要である。しかし,酸化LDLの詳細な発生機構は不明である。生体内ではLDLの酸化が単なる自動酸化ではなく,脂肪酸の種類や位置特異性を示す酵素が関与することが示されている。このような不飽和脂肪酸の特異的酸化を触媒する酵素としては,リポキシゲナーゼしかない。そこで,12/15-リポキシゲナーゼの動脈硬化発症における病態生理機能の解明を目的として,この酵素をマウスマクロファージ様J774A.1細胞に過剰発現させて実験を行った。12/15-リポキシゲナーゼを過剰発現する細胞によってLDLが酵素的に酸化されること,この酸化LDLはスカベンジャー受容体に認識されることを明らかにした。さらに,細胞内に存在する12/15-リポキシゲナーゼによる血清中のLDLの酸化には,LDL受容体やスカベンジャー受容体ではなく,LRP(LDL receptor-related protein)が関与することを明らかにした。このマクロファージのLRPを介した12/15-リポキシゲナーゼによるLDL酸化機構を詳細に解析したところ,LRPがLDL粒子を細胞内に取り込むのではなく,LDL粒子中のコレステロールエステルのみを細胞膜に選択的に取り込むことが示唆された。さらに,抗12/15-リポキシゲナーゼ抗体を用いた実験により,この酵素が細胞質から細胞膜にトランスロケーションすることが示された。","subitem_description_type":"Abstract"},{"subitem_description":"Lipoxygenase incorporates a molecular oxygen regiospecifically and stereospeciflcally into unsaturated fatty acids. There are four classes of enzymes in mammalian tissues; 5-, 8-, 12-, and 15-lipoxygenases, named by the number indicating oxygenation site of arachidonic acid as a substrate. Among the enzymes, 12-lipoxygenases are widely distributed in various tissues and species, and there are three isoforms: platelet, leukocyte and epidermis types. Since the leukocyte 12-lipoxygenase and 15-lipoxygenase-1 are highly related in their primary structures and enzymological properties, these enzymes are collectively called as 12/15-lipoxygenase. A number of evidences support the role of 12/15-lipoxygenase in LDL oxidation. In order to investigate precise mechanisms of the 12/15-lipoxygenase-mediated LDL oxidation, we established a mouse macrophage-like J774A1 cell line overexpressing porcine leukocyte 12-lipoxygenase. The presence of regio- and stereospeciflcally oxygenated product of cholesteryl linoleate in the LDL indicates that the 12/15-lipoxygenase is responsible for cell-mediated LDL oxidation. We also showed that LDL receptor-related protein (LRP) was required for the enzyme-mediated LDL oxidation by macrophages. Furthermore, cholesterol ester selectively transferred from the LDL particle to the plasma membrane via LRP is oxygenated by 12/15-lipoxygenase translocated to this membrane:","subitem_description_type":"Abstract"}]},"item_9_description_22":{"attribute_name":"内容記述","attribute_value_mlt":[{"subitem_description":"研究課題/領域番号:12470024, 研究期間(年度):2000 – 2002","subitem_description_type":"Other"},{"subitem_description":"出典：「12/15-リポキシゲナーゼで合成される脂質シグナル分子の病態生理機能」研究成果報告書　課題番号12470024\n（KAKEN：科学研究費助成事業データベース（国立情報学研究所））\n（https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-12470024/)を加工して作成","subitem_description_type":"Other"}]},"item_9_description_5":{"attribute_name":"提供者所属","attribute_value_mlt":[{"subitem_description":"金沢大学大学院・医学系研究科","subitem_description_type":"Other"}]},"item_9_identifier_registration":{"attribute_name":"ID登録","attribute_value_mlt":[{"subitem_identifier_reg_text":"10.24517/00063523","subitem_identifier_reg_type":"JaLC"}]},"item_9_relation_28":{"attribute_name":"関連URI","attribute_value_mlt":[{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/ja/search/?kw=60127876"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/ja/search/?kw=60127876","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-12470024/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-12470024/","subitem_relation_type_select":"URI"}}]},"item_9_version_type_25":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_ab4af688f83e57aa","subitem_version_type":"AM"}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2021-08-26"}],"displaytype":"detail","filename":"ME-PR-YOSHIMOTO-T-kaken 2004-2p.pdf","filesize":[{"value":"106.1 kB"}],"format":"application/pdf","licensetype":"license_11","mimetype":"application/pdf","url":{"label":"ME-PR-YOSHIMOTO-T-kaken 2004-2p.pdf","url":"https://kanazawa-u.repo.nii.ac.jp/record/57253/files/ME-PR-YOSHIMOTO-T-kaken 2004-2p.pdf"},"version_id":"5c634276-4617-42b4-a221-3aae3cc7af48"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"jpn"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"research report","resourceuri":"http://purl.org/coar/resource_type/c_18ws"}]},"item_title":"12/15-リポキシゲナーゼで合成される脂質シグナル分子の病態生理機能","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"12/15-リポキシゲナーゼで合成される脂質シグナル分子の病態生理機能"},{"subitem_title":"Pathophysiological role of lipid molecules produced by 12/l5-lipoxygenase","subitem_title_language":"en"}]},"item_type_id":"9","owner":"18","path":["2831"],"pubdate":{"attribute_name":"公開日","attribute_value":"2021-08-26"},"publish_date":"2021-08-26","publish_status":"0","recid":"57253","relation_version_is_last":true,"title":["12/15-リポキシゲナーゼで合成される脂質シグナル分子の病態生理機能"],"weko_creator_id":"18","weko_shared_id":-1},"updated":"2023-07-27T14:40:10.781052+00:00"}