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HCV core protein plays important roles in HCV-related hepatocarcinogenesis, because mice carrying the core protein exhibit multicentric HCCs without hepatic inflammation and fibrosis. However, the precise mechanism of hepatocarcinogenesis in these transgenic mice remains unclear. To evaluate whether the core protein modulates hepatocyte proliferation and apoptosis in vivo, we examined these parameters in 9- and 22-month-old transgenic mice. Although the numbers of apoptotic hepatocytes and hepatic caspase 3 activities were similar between transgenic and nontransgenic mice, the numbers of proliferating hepatocytes and the levels of numerous proteins such as cyclin D1, cyclin-dependent kinase 4 and c-Myc, were markedly increased in an age-dependent manner in the transgenic mice. This increase was correlated with the activation of peroxisome proliferator-activated receptor alpha (PPAR alpha). In these transgenic mice, spontaneous and persistent PPAR alpha activation occurred heterogeneously, which was different from that observed in mice treated with clofibrate, a potent peroxisome proliferator. We further demonstrated that stabilization of PPAR alpha through a possible interaction with HCV core protein and an increase in nonesterified fatty acids, which may serve as endogenous PPAR alpha ligands, in hepatocyte nuclei contributed to the core protein-specific PPAR alpha activation. In conclusion, these results offer the first suggestion that HCV core protein induces spontaneous, persistent, age-dependent and heterogeneous activation of PPAR alpha in transgenic mice, which may contribute to the age-dependent and multicentric hepatocarcinogenesis mediated by the core protein. (C) 2007 Wiley-Liss, Inc."}]}, "item_creator": {"attribute_name": "著者", "attribute_type": "creator", "attribute_value_mlt": [{"creatorNames": [{"creatorName": "Tanaka, N", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "8508", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Moriya, K", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "8509", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Kiyosawa, K", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "8510", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Koike, K", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "8511", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Aoyama, T", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "8512", "nameIdentifierScheme": "WEKO"}]}]}, "item_files": {"attribute_name": "ファイル情報", "attribute_type": "file", "attribute_value_mlt": [{"accessrole": "open_date", "date": [{"dateType": "Available", "dateValue": "2015-09-24"}], "displaytype": "detail", "download_preview_message": "", "file_order": 0, "filename": "ManuscriptR200705.pdf", "filesize": [{"value": "309.9 kB"}], "format": "application/pdf", "future_date_message": "", "is_thumbnail": false, "licensetype": "license_note", "mimetype": "application/pdf", "size": 309900.0, "url": {"label": "ManuscriptR200705.pdf", "url": "https://soar-ir.repo.nii.ac.jp/record/3999/files/ManuscriptR200705.pdf"}, "version_id": "1e77e1e9-79cc-4c6f-b5f2-4c9c4c3800de"}]}, "item_language": {"attribute_name": "言語", "attribute_value_mlt": [{"subitem_language": "eng"}]}, "item_resource_type": {"attribute_name": "資源タイプ", "attribute_value_mlt": [{"resourcetype": "journal article", "resourceuri": "http://purl.org/coar/resource_type/c_6501"}]}, "item_title": "Hepatitis C virus core protein induces spontaneous and persistent activation of peroxisome proliferator-activated receptor alpha in transgenic mice: Implications for HCV-associated hepatocarcinogenesis", "item_titles": {"attribute_name": "タイトル", "attribute_value_mlt": [{"subitem_title": "Hepatitis C virus core protein induces spontaneous and persistent activation of peroxisome proliferator-activated receptor alpha in transgenic mice: Implications for HCV-associated hepatocarcinogenesis", "subitem_title_language": "en"}]}, "item_type_id": "6", "owner": "1", "path": ["462"], "permalink_uri": "http://hdl.handle.net/10091/930", "pubdate": {"attribute_name": "PubDate", "attribute_value": "2008-01-21"}, "publish_date": "2008-01-21", "publish_status": "0", "recid": "3999", "relation": {}, "relation_version_is_last": true, "title": ["Hepatitis C virus core protein induces spontaneous and persistent activation of peroxisome proliferator-activated receptor alpha in transgenic mice: Implications for HCV-associated hepatocarcinogenesis"], "weko_shared_id": -1}
Hepatitis C virus core protein induces spontaneous and persistent activation of peroxisome proliferator-activated receptor alpha in transgenic mice: Implications for HCV-associated hepatocarcinogenesis
http://hdl.handle.net/10091/930
http://hdl.handle.net/10091/930eb88dbb5-bc56-428c-83c6-813eebc3d089
名前 / ファイル | ライセンス | アクション |
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Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2008-01-21 | |||||
タイトル | ||||||
言語 | en | |||||
タイトル | Hepatitis C virus core protein induces spontaneous and persistent activation of peroxisome proliferator-activated receptor alpha in transgenic mice: Implications for HCV-associated hepatocarcinogenesis | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源 | http://purl.org/coar/resource_type/c_6501 | |||||
タイプ | journal article | |||||
著者 |
Tanaka, N
× Tanaka, N× Moriya, K× Kiyosawa, K× Koike, K× Aoyama, T |
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出版者 | ||||||
出版者 | WILEY-LISS | |||||
引用 | ||||||
内容記述タイプ | Other | |||||
内容記述 | INTERNATIONAL JOURNAL OF CANCER. 122(1): 124-131 | |||||
書誌情報 |
INTERNATIONAL JOURNAL OF CANCER 巻 122, 号 1, p. 124-131, 発行日 2008-01-01 |
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内容記述 | ||||||
内容記述タイプ | Other | |||||
内容記述 | This is a preprint of an article published in INTERNATIONAL JOURNAL OF CANCER. Copyright (c) 2008 Wiley-Liss, Inc., A Wiley Company | |||||
資源タイプ(コンテンツの種類) | ||||||
内容記述タイプ | Other | |||||
内容記述 | Article | |||||
ISSN | ||||||
収録物識別子タイプ | PISSN | |||||
収録物識別子 | 0020-7136 | |||||
書誌レコードID | ||||||
収録物識別子タイプ | NCID | |||||
収録物識別子 | AA00680002 | |||||
他の資源との関係:URI | ||||||
識別子タイプ | URI | |||||
関連識別子 | http://www3.interscience.wiley.com/cgi-bin/jhome/29331 | |||||
関連名称 | http://www3.interscience.wiley.com/cgi-bin/jhome/29331 | |||||
DOI | ||||||
識別子タイプ | DOI | |||||
関連識別子 | https://doi.org/10.1002/ijc.23056 | |||||
関連名称 | 10.1002/ijc.23056 | |||||
出版タイプ | ||||||
出版タイプ | AM | |||||
出版タイプResource | http://purl.org/coar/version/c_ab4af688f83e57aa | |||||
WoS | ||||||
表示名 | Web of Science | |||||
URL | http://gateway.isiknowledge.com/gateway/Gateway.cgi?&GWVersion=2&SrcAuth=ShinshuUniv&SrcApp=ShinshuUniv&DestLinkType=FullRecord&DestApp=WOS&KeyUT=000251193700016 |