{"created":"2023-07-27T06:58:45.256356+00:00","id":57775,"links":{},"metadata":{"_buckets":{"deposit":"43ed72e7-ad1f-4697-9cff-16af2d9e5c07"},"_deposit":{"created_by":18,"id":"57775","owners":[18],"pid":{"revision_id":0,"type":"depid","value":"57775"},"status":"published"},"_oai":{"id":"oai:kanazawa-u.repo.nii.ac.jp:00057775","sets":["2812:2813:2834"]},"author_link":["185"],"item_9_biblio_info_8":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2001-10-22","bibliographicIssueDateType":"Issued"},"bibliographicPageStart":"2p.","bibliographicVolumeNumber":"1998 – 1999","bibliographic_titles":[{"bibliographic_title":"平成11(1999)年度 科学研究費補助金 基盤研究(C) 研究成果報告書概要"},{"bibliographic_title":"1999 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":"アラキドン酸から12/15-リポキシゲナーゼによって合成されるヒドロペルオキシ酸がc-fosやc-junなどの転写調節因子の発現を誘導し,Mitogen-activated protein(MAP)キナーゼを活性化することによって,マクロファージや平滑筋細胞の増殖に関与している。臨床的にも動脈硬化症などの疾患にリポキシゲナーゼが関与していることが示唆されている。本研究では,動脈硬化症の初期病変に関与する低比重リポタンパク質(LDL)の酸化機構において,細胞内の12-リポキシゲナーゼが果たす役割を明らかにすることを目的として,遺伝子発現系を用いて解析した。伸張因子1-αの強力なプロモーターを有する発現ベクターpEF-BOSに,ネオマイシン耐性遺伝子を組み込んだ後,LDLに対する反応性が異なる白血球型および血小板型の12-リポキシゲナーゼcDNAを組み込んだ。この発現ベクターを,マウスマクロファージ様J774A.1細胞にリポフェクタミン法で導入して安定形質発現株を確立した。12-リポキシゲナーゼ発現細胞株のいずれの酵素型でもLDL内に酸化脂質の増加が認められ,その酸化脂質の分子種を高速液体クロマトグラフィーで解析するによって,酵素的にLDLの酸化がおこることが示された。さらに,この12-リポキシゲナーゼ発現細胞で産生された酸化LDLは,マクロファージのスカベンジャー受容体に認識されることが示された。これらの実験結果は,マクロファージに多量に存在する12-リポキシゲナーゼがLDLを酸化し,動脈硬化の発症に深く関与していることを示唆するものである。","subitem_description_type":"Abstract"},{"subitem_description":"Lipoxygenase (LOX) incorporates a molecular oxygen into a specific carbon atom of unsaturated fatty acids. There are 5-, 8-, 12- and 15-LOXs in mammalian tissues according to the oxygenation site of arachidonic acid. Based upon the primary structures deduced from their cDNAs and enzymological properties, they are principally classified into 5-LOX and 12/15-LOX subfamilies. The 5-LOX catalyzes the first step in the generation of leukotrienes which have potent biological activities in the immediate hypersensitivity and allergy. There are number of isoforms of 12/15-LOXs : leukocyte, platelet and epidermis. Although the 12/15-LOXs have been shown to play roles in several systems such as atherosclerosis and neurotransmission, their pathophysiological functions are still subjects of investigation and discussion.\nThere are a body of circumstantial evidences for a role of LOX in oxidative modification of low density lipoprotein (LDL). The aim of this study was to investigate the role of intracellular 12-LOX in the oxidative modification of LDL that leads to foam cell formation. We overexpressed 12-lipoxygenases in a macrophage-like cell line J774A.1 which originally did not show the detectable enzyme activity. When the 12-lipoxygenase-expressing cells were incubated with LDL in Dulbecco's modified Eagle medium at 37 ℃ for 12 h, LDL oxidation as determined by thiobarbituric acid reactive substance was markedly increased over the mock-transfected cells. Oxygenated products in the modified LDL were examined by high performance liquid chromatography before and after alkaline hydrolysis. Most of the oxygenated derivatives were of an esterified form, and the major product was identified to be 13S-hydroxyoctadeca-9Z, 11E-dienoic acid. These results clearly demonstrated that esterified fatty acids in LDL were oxygenated by the 12-lipoxygenases expressed in the J774A.1 cells. Furthermore, the oxidized LDL generated by intracellular 12-lipoxygenases was recognized by a scavenger receptor as assessed by macrophage degradation assay.","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:10670134, 研究期間(年度):1998 – 1999","subitem_description_type":"Other"},{"subitem_description":"出典：「12/15-リポキシゲナーゼアイソザイムの組織特異的発現と細胞増殖機構」研究成果報告書　課題番号10670134\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/report/KAKENHI-PROJECT-10670134/106701341999kenkyu_seika_hokoku_gaiyo/）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":"金沢大学医学部","subitem_description_type":"Other"}]},"item_9_identifier_registration":{"attribute_name":"ID登録","attribute_value_mlt":[{"subitem_identifier_reg_text":"10.24517/00064045","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-10670134/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-10670134/","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/ja/report/KAKENHI-PROJECT-10670134/106701341999kenkyu_seika_hokoku_gaiyo/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/ja/report/KAKENHI-PROJECT-10670134/106701341999kenkyu_seika_hokoku_gaiyo/","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":"2021-09-06"}],"displaytype":"detail","filename":"ME-PR-YOSHIMOTO-T-kaken 2001-2p.pdf","filesize":[{"value":"89.2 kB"}],"format":"application/pdf","licensetype":"license_11","mimetype":"application/pdf","url":{"label":"ME-PR-YOSHIMOTO-T-kaken 2001-2p.pdf","url":"https://kanazawa-u.repo.nii.ac.jp/record/57775/files/ME-PR-YOSHIMOTO-T-kaken 2001-2p.pdf"},"version_id":"1f87bec9-c38b-496f-a577-7fcbae1b82c3"}]},"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-リポキシゲナーゼアイソザイムの組織特異的発現と細胞増殖機構","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"12/15-リポキシゲナーゼアイソザイムの組織特異的発現と細胞増殖機構"},{"subitem_title":"Mechanisms for tissue specific expression and cell growth of 12/15-lipoxygenase","subitem_title_language":"en"}]},"item_type_id":"9","owner":"18","path":["2834"],"pubdate":{"attribute_name":"公開日","attribute_value":"2021-09-06"},"publish_date":"2021-09-06","publish_status":"0","recid":"57775","relation_version_is_last":true,"title":["12/15-リポキシゲナーゼアイソザイムの組織特異的発現と細胞増殖機構"],"weko_creator_id":"18","weko_shared_id":-1},"updated":"2023-07-27T14:55:18.438763+00:00"}