{"created":"2023-06-20T16:43:12.790465+00:00","id":14033,"links":{},"metadata":{"_buckets":{"deposit":"d6de609a-65d2-451a-992f-e92e4a9f92dd"},"_deposit":{"created_by":3,"id":"14033","owners":[3],"pid":{"revision_id":0,"type":"depid","value":"14033"},"status":"published"},"_oai":{"id":"oai:kindai.repo.nii.ac.jp:00014033","sets":["14:2667:2671:2672"]},"author_link":["3865"],"item_8_alternative_title_3":{"attribute_name":"その他（別言語等）のタイトル","attribute_value_mlt":[{"subitem_alternative_title":"Regulation of PPARg by endogenous metabolites in health and disease"}]},"item_8_biblio_info_21":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2013-01-01","bibliographicIssueDateType":"Issued"},"bibliographicPageEnd":"5","bibliographicPageStart":"1","bibliographic_titles":[{"bibliographic_title":"科学研究費助成事業研究成果報告書 (2013. )"}]}]},"item_8_description_33":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"研究成果の概要(和文): 核内受容体PPARγアゴニストによる2型糖尿病治療効果が明確であるにもかかわらず, 生活習慣病においてPPARγがどのように疾患に関与しているのかは不明である. 本研究では, 精製したリコンビナントPPARγに, ヘム合成の中間代謝物がPPARγに共有結合していることを発見した. 遺伝性にヘム合成が充進しているEPP患者で見っかったヘム合成の律速酵素ALAS2の変異遺伝子を用い, ヘム合成を充進した細胞を構築したところ, 共培養したマクロファージ細胞株THP-1におけるPPARγ活性が阻害された. 従って, 疾患においてヘム合成中間代謝物がPPARγを阻害する事で生活習慣病の進行を引き起こしている可能性が示された.           研究成果の概要 (英文): Erythropoietic protoporphyria (EPP) patients show higher risk of metabolic syndrome such as atherosclerosis with unknown reason. Here, we found that the inhibition of the peroxisome proliferator-activated receptor γ (PPARγ) by anerythroid-derived heme-related metabolite. Using the EPP cells expressing ALAS2 gene with dominant mutation (called as ALAS2delAT), we observed the perturbation of PPARγactivity in co-cultured THP-1 macrophage cells. Phagocytosis-mediated application of exogenous heme-related metabolite complex to the THP-1 cells mimicked the effects of EPP cells. We also found that it covalently bound to the Cys285 in the PPARγ LBD. Thus, this heme-related metabolite is the endogenous risk factor for the metabolic syndrome through the PPARγ inhibition.","subitem_description_type":"Abstract"}]},"item_8_description_36":{"attribute_name":"内容記述","attribute_value_mlt":[{"subitem_description":"研究種目：新学術領域研究;  研究期間：2012～2013;   課題番号：24116524;   研究分野：医歯薬学;   科研費の分科・細目：基礎医学・医化学一般","subitem_description_type":"Other"}]},"item_8_description_37":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"subitem_description":"Research Paper","subitem_description_type":"Other"}]},"item_8_description_41":{"attribute_name":"フォーマット","attribute_value_mlt":[{"subitem_description":"application/pdf","subitem_description_type":"Other"}]},"item_8_publisher_14":{"attribute_name":"出版者 名前","attribute_value_mlt":[{"subitem_publisher":"近畿大学"}]},"item_8_relation_11":{"attribute_name":"著者 外部リンク","attribute_value_mlt":[{"subitem_relation_name":[{"subitem_relation_name_text":"http://kaken.nii.ac.jp/d/r/10311747.ja.html"}]}]},"item_8_text_10":{"attribute_name":"著者 役割","attribute_value_mlt":[{"subitem_text_value":"研究代表者"}]},"item_8_text_7":{"attribute_name":"著者(英)","attribute_value_mlt":[{"subitem_text_language":"en","subitem_text_value":"SHIRAKI, TAKUMA"}]},"item_8_text_8":{"attribute_name":"著者 所属","attribute_value_mlt":[{"subitem_text_value":"近畿大学生物理工学部; 准教授"}]},"item_8_version_type_12":{"attribute_name":"版","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_970fb48d4fbd8a85","subitem_version_type":"VoR"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"白木,  琢磨"},{"creatorName":"シラキ, タクマ","creatorNameLang":"ja-Kana"}],"nameIdentifiers":[{},{}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2016-03-31"}],"displaytype":"detail","filename":"KAKEN_24116524seika.pdf","filesize":[{"value":"300.5 kB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"KAKEN_24116524seika.pdf","url":"https://kindai.repo.nii.ac.jp/record/14033/files/KAKEN_24116524seika.pdf"},"version_id":"62ab76e9-ae6d-4b2d-a5c5-c2f861633620"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"転写制御","subitem_subject_scheme":"Other"},{"subitem_subject":"生体内代謝物","subitem_subject_scheme":"Other"},{"subitem_subject":"生活習慣病","subitem_subject_scheme":"Other"}]},"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":"疾患において変動する代謝物リガンドによる核内受容体PPARg の機能制御","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"疾患において変動する代謝物リガンドによる核内受容体PPARg の機能制御"}]},"item_type_id":"8","owner":"3","path":["2672"],"pubdate":{"attribute_name":"公開日","attribute_value":"2014-10-02"},"publish_date":"2014-10-02","publish_status":"0","recid":"14033","relation_version_is_last":true,"title":["疾患において変動する代謝物リガンドによる核内受容体PPARg の機能制御"],"weko_creator_id":"3","weko_shared_id":-1},"updated":"2023-06-20T23:04:13.461555+00:00"}