原発性胆汁性肝硬変の胆管病変におけるエネルギー代謝の解析と治療戦略

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Author: 原田, 憲一ほか

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Publication date: 2017-05-29

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Note (General)：: 金沢大学医薬保健研究域医学系原発性胆汁性胆管炎(肝硬変)(PBC)の胆管障害および胆管細胞死の発生に、解糖系から脂肪酸分解系へのエネルギー代謝へと誘導する分子であるperoxisome proliferator-activated receptor γ coactivator 1α (PGC-1α)...

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Material Type: 文書・図像類
Title: 原発性胆汁性肝硬変の胆管病変におけるエネルギー代謝の解析と治療戦略
Author/Editor: 原田, 憲一
Harada, Ken-ichi
Author Heading: 原田, 憲一
Harada, Ken-ichi
Publication Date: 2017-05-29
Publication Date (W3CDTF): 2017-05-29
Alternative Title: Alteration of energy metabolism in the pathogenesis of bile duct lesions in primary biliary cholangitis
Periodical title: 平成28(2016)年度科学研究費補助金基盤研究(C) 研究成果報告書 = 2016 Fiscal Year Final Research Report
No. or year of volume/issue: 2014-04-01 - 2017-03-31
Volume: 2014-04-01 - 2017-03-31
Pages: 6p.-
Text Language Code: jpn
Subject Heading: 原発性胆汁性胆管炎
慢性非化膿性破壊性胆管炎
代謝
Target Audience: 一般
Note (General): 金沢大学医薬保健研究域医学系
原発性胆汁性胆管炎(肝硬変)(PBC)の胆管障害および胆管細胞死の発生に、解糖系から脂肪酸分解系へのエネルギー代謝へと誘導する分子であるperoxisome proliferator-activated receptor γ coactivator 1α (PGC-1α)/estrogen-related receptorα(ERRα)の発現亢進、また酸化ストレスの亢進に起因するアポトーシス調節分子の発現亢進が関与することを明らかにした。解糖系から脂肪酸分解系へのエネルギー代謝の偏位に起因する酸化ストレス誘導性アポトーシス感受性の亢進がCNSDCから胆管消失に関与していると考えられた。
Primary biliary cholangitis (cirrhosis) (PBC) is characterized by chronic nonsuppurative destructive cholangitis (CNSDC). Estrogen-related receptor-α (ERRα) is functionally activated by inducible coactivators such as peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α). Moreover, the PGC-1α/ERRα axis interrupts glycolytic metabolism through the upregulation of pyruvate dehydrogenase kinase, isozyme 4 (PDK4), which functionally inhibits PDC-E1α and stimulates fatty acid oxidation. In this study, we clarified that, in CNSDC of PBC, the activation of the ERRα/PGC-1α axis was exclusively observed, suggesting the interference of PDC-related glycolytic function and the induction of the fatty acid degradation system. Moreover, upregulation of oxidative stress, proapoptotic molecules, and apopsosis are shown in CNSDC. These suggest that the switching of the cellular energy system is possibly associated with the pathogenesis of CNSDC in PBC.
研究課題/領域番号:26460416, 研究期間(年度):2014-04-01 - 2017-03-31
DOI: 10.24517/00050994
Source: https://kanazawa-u.repo.nii.ac.jp/?action=repository_action_common_download&item_id=44653&item_no=1&attribute_id=26&file_no=1
https://kanazawa-u.repo.nii.ac.jp/?action=repository_action_common_download&item_id=44653&item_no=1&attribute_id=26&file_no=1
Access Restrictions: 限定公開
Rights (production): CC BY-NC-ND
Related Material: https://kaken.nii.ac.jp/search/?qm=30283112
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-26460416/
https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-26460416/26460416seika/
Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）
https://irdb.nii.ac.jp
Original Data Provider (Database): 金沢大学 : 金沢大学学術情報リポジトリKURA