{"created":"2023-07-27T06:50:22.224248+00:00","id":43122,"links":{},"metadata":{"_buckets":{"deposit":"7fbe4aae-dc74-4861-a0a8-c1da68ee89e0"},"_deposit":{"created_by":18,"id":"43122","owners":[18],"pid":{"revision_id":0,"type":"depid","value":"43122"},"status":"published"},"_oai":{"id":"oai:kanazawa-u.repo.nii.ac.jp:00043122","sets":["2812:2813:2833"]},"author_link":["69342","69343"],"item_9_biblio_info_8":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2001-03","bibliographicIssueDateType":"Issued"},"bibliographicPageStart":"11p.","bibliographicVolumeNumber":"1999-2000","bibliographic_titles":[{"bibliographic_title":"平成12(2000)年度 科学研究費補助金 基盤研究(C) 研究成果報告書"},{"bibliographic_title":"2000 Fiscal Year Final Research Report","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":"カルニチン欠乏症は、最終的には心機能異常など致死的症状を示す病態であるが、主に遺伝性の全身性カルニチン欠乏症と、また臨床的な薬物投与や食事等栄養状態による二次性カルニチン欠乏症に分けられる。本研究では二次性カルニチン欠乏症の中で、薬物誘導型カルニチン欠乏症におけるOCTN2の寄与の可能性について、腎を中心とした臓器におけるOCTN2の有機カチオン輸送や薬物によるカルニチン輸送活性変動について解析を行うことにより、OCTNトランスポーターの生理的・薬物動態的役割ならびにカルニチン欠乏症との関連について解析を行った。ヒトならびにマウスOCTN2は、カルニチンをNa^+依存的に、有機カチオンの一種であるテトラエチルアンモニウム(TEA)をNa^+非依存的に輸送した。また、TEA以外にもメピラミンやベラパミル及びキニジンなどのカチオン性薬物を輸送した。一方、これらカチオン性化合物に加え、中性ならびにアニオン性化合物によってもカルニチン輸送活性は機能阻害を受けた。OCTN2が存在する腎臓においては、カルニチンはNa^+を駆動力とした再吸収に働くが、このような臨床的に使われる医薬品によって機能阻害を受けるということは、薬物誘導型の二次性のカルニチン欠乏症発症原因の一つとしてOCTN2が関与することを示すものであることが明らかになった。一方、他のOCTNメンバーOCTN1ならびにマウスOCTN3についても解析を行った結果、OCTN3精巣特異的な発現であり、またOCTN1は低いカルニチン輸送活性しか有せず、全身性カルニチン欠乏症としてはOCTN2が最も重要であることが示唆された。","subitem_description_type":"Abstract"},{"subitem_description":"In the present study, novel Na^+-dependent carnitine/organic cation transporter family, OCTNs from human and mouse were identified and functionally characterized. We isolated two and three members of OCTN family from human and mouse, respectively. OCTNs are present in various tissues, including kidney, heart, skeletal muscle and placenta strongly, and in several human-derived cancer cell lines. By immunohistochemical analysis in kidney, mouse OCTNs localized commonly in luminal membrane of tubular epithelial cells. Most of human and mouse OCTNs exhibited multifunctionality by transporting both of carnitine and organic cation, tetraethylammonium (TEA). Furthermore, sodium ions were essential for carnitine transport by human and mouse OCTN1 and 2. In systemic carnitine deficiency (SCD) phenotype mouse model, juvenile visceral steotosis (jvs) mouse, mutation in OCTN2 gene was found. Furthermore, several kinds of mutation in human SCD patients were found, demonstrating that OCTN2 is a physiologically important carnitine transporter. Interestingly, TEA transport was sodium independent. In addition, OCTNs transporterd various cationic drugs such as quinidine, verapamil, and actinomycin D.Furthermore, since one mutation of human OCTN2 lost carnitine transport activity but retained TEA transport activity, it was suggested that OCTN2 have differential functional sites for carnitine and organic cations. So, OCTNs are thought to be multifunctional transporters by transporting carnitine and organic cations by sodium ion dependent and independent manner, respectively, and would be important for disposition of organic cationic drugs as well as carnitine. Furthermore, since carnitine transport via OCTN2 is inhibited various compounds, including organic cations, organic anions such as valproic acid and neutral compound such as cortisole, it is anticipated that drug-induced secondary carnitine deficiency could be caused by interaction on OCTN2.","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:11672212, 研究期間(年度):1999-2000","subitem_description_type":"Other"},{"subitem_description":"出典：「高親和性カルニチントランスポーターの機能特性と薬物誘導型毒性発症機構との関連」研究成果報告書　課題番号11672212\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　　　本文データは著者版報告書より作成","subitem_description_type":"Other"}]},"item_9_description_5":{"attribute_name":"提供者所属","attribute_value_mlt":[{"subitem_description":"金沢大学大学院自然科学研究科","subitem_description_type":"Other"}]},"item_9_identifier_registration":{"attribute_name":"ID登録","attribute_value_mlt":[{"subitem_identifier_reg_text":"10.24517/00049469","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/search/?qm=20155237"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/search/?qm=20155237","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11672212/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11672212/","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-11672212/116722122000kenkyu_seika_hokoku_gaiyo/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-11672212/116722122000kenkyu_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":"2017-12-21"}],"displaytype":"detail","filename":"PH-PR-TAMAI-I-kaken 2001-11p.pdf","filesize":[{"value":"406.6 kB"}],"format":"application/pdf","licensetype":"license_11","mimetype":"application/pdf","url":{"label":"PH-PR-TAMAI-I-kaken 2001-11p.pdf","url":"https://kanazawa-u.repo.nii.ac.jp/record/43122/files/PH-PR-TAMAI-I-kaken 2001-11p.pdf"},"version_id":"b1633711-221e-43f1-8968-d3a9a3abbfc7"}]},"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":"高親和性カルニチントランスポーターの機能特性と薬物誘導型毒性発症機構との関連","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"高親和性カルニチントランスポーターの機能特性と薬物誘導型毒性発症機構との関連"},{"subitem_title":"Functional characterization and relevance of carnitine transporter OCTN2 to secondary carnitine deficiency","subitem_title_language":"en"}]},"item_type_id":"9","owner":"18","path":["2833"],"pubdate":{"attribute_name":"公開日","attribute_value":"2017-12-21"},"publish_date":"2017-12-21","publish_status":"0","recid":"43122","relation_version_is_last":true,"title":["高親和性カルニチントランスポーターの機能特性と薬物誘導型毒性発症機構との関連"],"weko_creator_id":"18","weko_shared_id":-1},"updated":"2023-07-27T14:46:29.485000+00:00"}