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Association of between HCV induced mitochondria dysfunction and viral response by interferon in hepatic iron overloaded

Research Project

Project/Area Number 22590750
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionResearch Institute, International Medical Center of Japan (2011-2012)
Kawasaki Medical School (2010)

Principal Investigator

KORENAGA Masaaki  独立行政法人国立国際医療研究センター (70420536)

Co-Investigator(Kenkyū-buntansha) HINO Keisuke  川崎医科大学, 肝胆膵内科学, 教授 (80228741)
KORENAGA Keiko  国府台病院, 消化器・肝臓内科, 医師 (60420535)
Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2012: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2010: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywordsミトコンドリア / 鉄過剰状態 / 肝発癌 / 酸化ストレス / MAVS / IFN / C型慢性肝炎 / Hepcidin / PolyIC
Research Abstract

We previously reported that HCC developed through the oxidative stress in iron-overloaded transgenic mice expressing the hepatitis C virus (HCV) polyprotein (HCV TgM) (Gastroenterology;130: 2006) Oxidative stress is one of the pathophysiologic mechanisms involved in HCV-associated liver injury and hepatocarcinogenesis. The aim of this study was to clarify whether iron-induced oxidative stress affects HCV replication in full genomic HCV replicon cells. Methods: Various concentration of Fe(II)SO4, Fe(III)(NO3)3, FeCl2, FeCl3, Holo-transferrin apo-transferring or IFNα was added to the genome length HCV-RNA replicon (OR6) cells. Using reporter assay system, HCV replication was assessed. We also measured cellular reactive oxygen sepsis (ROS) production by DCF assay and the expression levels of HCV core protein by western blot. Result:Ferrous and ferric ions significantly inhibited HCV replication and the levels of core protein at the concentration of iron less than 1uM. However, only ferrous ions increased ROS production, suggesting that ferric ions may have inhibited HCV replication through its cytotoxicity Additional IFN treatment showed additive inhibition of HCV replication. Conclusion: Although iron- induced oxidative stress accelerates hepatocarcinogenesis, it may work as an anti-HCV factor in patients with chronic hepatitis C. These data suggested that we should avoid touse antioxidant agents during IFN therapy.

Report

(4 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (41 results)

All 2013 2012 2011 2010

All Journal Article (15 results) (of which Peer Reviewed: 4 results) Presentation (23 results) Book (3 results)

  • [Journal Article] Clinical usefulness of non-protein respiratory quotient measurement in non-alcoholic fatty liver disease2013

    • Author(s)
      Korenaga K, Korenaga M, et al.
    • Journal Title

      Hepatol Res

      Volume: (In press)

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ex vivo induction of IFN-λ3 by a TLR7 agonist determines response to Peg-IFN/Ribavirin therapy in chronic hepatitis C patients.2013

    • Author(s)
      Murata K, Korenaga M, et al.
    • Journal Title

      J Gastroenterol

      Volume: (In press)

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Genome-wide association study confirming association of HLA-DP with protection against chronic hepatitis B and viral clearance in Japanese and Korean2012

    • Author(s)
      Nishida N, Korenaga M, Mizokami M, 他33名
    • Journal Title

      PLoS One

      Volume: 7(6)

    • Related Report
      2012 Final Research Report
  • [Journal Article] No association for Chinese HBV-related hepatocellular carcinoma susceptibility SNP in other East Asian populations.2012

    • Author(s)
      Sawai H, Korenaga M, Mizokami M, 他32名
    • Journal Title

      BMC Med Genet

      Volume: 19;13 Pages: 47-47

    • Related Report
      2012 Final Research Report
  • [Journal Article] LecT-Hepa, a glyco-marker derived from multiple lectins, as a predictor of liver fibrosis in chronic hepatitis C patients.2012

    • Author(s)
      Ito K, Korenaga M, Mizokami M, 他17名
    • Journal Title

      Hepatology

      Volume: 56 Pages: 1448-56

    • Related Report
      2012 Final Research Report
  • [Journal Article] 症例13 メトホルミンと瀉血が有効だった症例.2012

    • Author(s)
      是永匡紹, 是永圭子, 日野啓輔, 溝上雅史
    • Journal Title

      症例に学ぶNASH/NAFLDの診断と治療―臨床で役立つ症例 (岡上武, 米田正人, 江口有一郎, 角田圭雄, 中島淳編集, 診断と治療社, 東京)

      Volume: 32

    • Related Report
      2012 Final Research Report
  • [Journal Article] C型肝炎の肝発癌と発癌抑制(インターフェロン少量/ウルソ/SNMC/BCAAなど).2012

    • Author(s)
      是永匡紹, 溝上雅史
    • Journal Title

      肝炎ウイルス-B型・C型 インフォームドコンセントのための図説シリーズ (熊田博光編集, 医薬ジャーナル社, 大阪)

      Pages: 100-105

    • Related Report
      2012 Final Research Report
  • [Journal Article] 肝硬変に対する治療.2012

    • Author(s)
      是永匡紹, 溝上雅史
    • Journal Title

      最新 C型肝炎 治療薬の使い方 (芥田憲夫, 斉藤聡, 角田圭雄編集, 診断と治療社, 東京)

      Pages: 46-54

    • Related Report
      2012 Final Research Report
  • [Journal Article] HCV感染における鉄過剰異常、酸化ストレスと分岐鎖アミノ酸2012

    • Author(s)
      是永匡紹、日野啓輔, 溝上雅史
    • Journal Title

      肝がん・肝硬変に対する栄養療法の新時代 (市田隆文、平野 克治監・編集, アークメディア 東京)

      Pages: 16-19

    • Related Report
      2012 Final Research Report
  • [Journal Article] A glycyrrhizin-containing preparation reduces hepatic steatosis induced by hepatitis C virus protein and iron in mice.2011

    • Author(s)
      Korenaga M, Hidaka I, Hino K, 他7名
    • Journal Title

      Liver Int

      Volume: 31(4) Pages: 552-60

    • Related Report
      2012 Final Research Report
  • [Journal Article] A glycyrrhizin-containing preparation reduces hepatic steatosis induced by hepatitis C virus protein and iron in mice2011

    • Author(s)
      Korenaga M, et al
    • Journal Title

      Liver Int

      Volume: 31 Pages: 552-60

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 過剰鉄とミトコンドリア障害が誘導する酸化ストレスはC型肝炎ウイルス増殖を抑制する2011

    • Author(s)
      是永匡紹, 他
    • Journal Title

      酸化ストレスと肝疾患

      Volume: 7 Pages: 41-46

    • Related Report
      2011 Annual Research Report
  • [Journal Article] Hepatitis C virus protein and iron overload induce hepatic steatosis through the unfolded protein response in mice2010

    • Author(s)
      Nishina S, Korenaga M, Hino K, 他6名
    • Journal Title

      Liver Int

      Volume: 30(5) Pages: 683-92

    • Related Report
      2012 Final Research Report
  • [Journal Article] Hepatitis C virus protein and iron overload induce hepatic steatosis through the unfolded protein response in mice2010

    • Author(s)
      Nishina S, Korenaga M, et al
    • Journal Title

      Liver Int.

      Volume: 30 Pages: 683-92

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] C型慢性肝炎のpeg-IFN/RBV療法無効例の対策】pegIFN/RBV療法無効例への工夫再燃・null例への再治療の試み2010

    • Author(s)
      是永匡紹, 他
    • Journal Title

      消化器内科

      Volume: 50 Pages: 595-600

    • Related Report
      2010 Annual Research Report
  • [Presentation] Anti-interferon-α neutralizing antibodies interact with viral responses to interferon in patients with hepatitis C virus infection bearing interferon sensitive IL28B single nucleotide polymorphisms.2012

    • Author(s)
      Korenaga M, Korenaga K, Nishina S, Yoshioka N, Tomiyama Y, Hara Y, Sugiyama M, Nishida N, Murata K, Masaki N, Mizokami M, Hino K.
    • Organizer
      The 63rd annual meeting of the American association for the study of liver diseases (AASLD)
    • Place of Presentation
      Boston, U.S.
    • Related Report
      2012 Final Research Report
  • [Presentation] Supplementation with branched-chain amino acids improves HCV-induced iron metabolic disorder via upregulation of antioxidant potential by restoring mitochondrial complex I function in iron overloaded transgenic mice expressing HCV polyprotein2012

    • Author(s)
      Korenaga M, Nishina S, Korenaga K, Tomiyama Y, Hara Y, Sakai Y, Shimonaka Y, Mizokami M, Hino K
    • Organizer
      The 63rd annual meeting of the American association for the study of liver diseases (AASLD)
    • Place of Presentation
      Boston, U.S.
    • Related Report
      2012 Final Research Report
  • [Presentation] IFN 少量長期投与はHCV 関連肝発癌における鉄代謝異常を改善する ワークショップ10 肝細胞癌の発症と再発予防を目指した慢性肝炎の治療2012

    • Author(s)
      是永匡紹、仁科惣治、是永圭子、日野啓輔
    • Organizer
      第48回日本肝臓総会
    • Place of Presentation
      金沢
    • Related Report
      2012 Final Research Report
  • [Presentation] HCVトランスジェニックマウスを用いた分枝鎖アミノ酸・インターフェロンの鉄代謝機構の解析2012

    • Author(s)
      是永匡紹, 他
    • Organizer
      第98回日本消化器病学会総会
    • Place of Presentation
      東京
    • Related Report
      2012 Annual Research Report
  • [Presentation] Amino acid Imbalance を有した高齢C型慢性肝疾患への有効性2012

    • Author(s)
      是永匡紹, 他
    • Organizer
      第48回 日本肝臓学会総会
    • Place of Presentation
      金沢
    • Related Report
      2012 Annual Research Report
  • [Presentation] IFN少量長期投与はHCVが誘導する鉄代謝異常を改善し肝発癌を抑制する2012

    • Author(s)
      是永匡紹, 他
    • Organizer
      第48回 日本肝臓学会総会
    • Place of Presentation
      金沢
    • Related Report
      2012 Annual Research Report
  • [Presentation] BTRを指標としたC型慢性肝疾患への治療介入2012

    • Author(s)
      是永匡紹, 他
    • Organizer
      第39回日本肝臓学会東部会
    • Place of Presentation
      東京
    • Related Report
      2012 Annual Research Report
  • [Presentation] The supplementation with branched-chain amino acids (BCAAS) reduces hepatic iron accumulation and oxidative stress in both transgenic mice and patients with HCV2012

    • Author(s)
      Korenaga M, et al.
    • Organizer
      14th International Symposium on Viral Hepatitis and liver Disease
    • Place of Presentation
      上海
    • Related Report
      2012 Annual Research Report
  • [Presentation] Supplementation with branched-chain amino acids improves HCV-induced iron metabolic disorder via upregulation of antioxidant potential by restoring mitochondrial complex I function in iron overloaded transgenic mice expressing HCV polyprotein2012

    • Author(s)
      Korenaga M, et al.
    • Organizer
      64 the AASLD (アメリカ肝臓学会)
    • Place of Presentation
      Boston USA
    • Related Report
      2012 Annual Research Report
  • [Presentation] Dietary supplementation with branched-chain amino acids reduces hepatic iron accumulation induced by hepatitis C virus proteins and iron overload in mice.2011

    • Author(s)
      Korenaga M, Korenaga K, Nishina S, Tomiyama Y, Hino K
    • Organizer
      The 62rd annual meeting of the American association for the study of liver diseases (AASLD)
    • Place of Presentation
      San Francisco, U.S.
    • Related Report
      2012 Final Research Report
  • [Presentation] Oral branched-chain amino acid supplementation reduces oxidative stress and interacts with iron metabolism in patients with hepatitis C virus-related advanced liver fibrosis -a pilot study-.2011

    • Author(s)
      Korenaga M, Korenaga K, Nishina S, Tomiyama Y, Hino K
    • Organizer
      The 62rd annual meeting of the American association for the study of liver diseases (AASLD)
    • Place of Presentation
      San Francisco, U.S.
    • Related Report
      2012 Final Research Report
  • [Presentation] テーラーメード医療時代のおける抗IFNα抗体測定の意義2011

    • Author(s)
      是永匡紹 是永圭子 日野啓輔
    • Organizer
      第39回日本肝臓学会西部会 シンポジウム1テーラーメード医療時代のC型肝炎治療戦略
    • Place of Presentation
      岡山
    • Related Report
      2012 Final Research Report
  • [Presentation] C型慢性肝疾患の鉄代謝異常に対するBCAA顆粒投与の有効性2011

    • Author(s)
      是永匡紹 是永圭子 日野啓輔
    • Organizer
      第15回日本肝臓学会大会 第53回日本消化器病学会大会 シンポジウム14 代謝性・遺伝性肝疾患研究の進歩
    • Place of Presentation
      福岡
    • Related Report
      2012 Final Research Report
  • [Presentation] BCAA顆粒はHCVTgMにおける肝内鉄過剰と酸化ストレスを抑制する2011

    • Author(s)
      是永匡紹, 仁科惣治, 田中志保, 是永圭子, 日野啓輔
    • Organizer
      第47回 日本肝臓学会総会 ワークショップ1「代謝・酸化ストレスの場としての肝臓」
    • Place of Presentation
      東京
    • Related Report
      2012 Final Research Report
  • [Presentation] 鉄負荷HCVTgMにおけるhepcidin25発現とサイトカインの網羅的解析2011

    • Author(s)
      是永匡紹, 田中志保, 佐々木雄亮, 下中靖, 日野啓輔
    • Organizer
      第97回日本消化器病学会総会
    • Place of Presentation
      東京
    • Related Report
      2012 Final Research Report 2011 Annual Research Report
  • [Presentation] BCAA顆粒はHCVTgMにおける肝内鉄過剰と酸化ストレスを抑制する2011

    • Author(s)
      是永匡紹, 他
    • Organizer
      第47回日本肝臓学会総会
    • Place of Presentation
      東京
    • Related Report
      2011 Annual Research Report
  • [Presentation] C型慢性肝疾患に対するBCAA顆粒投与と鉄代謝2011

    • Author(s)
      是永匡紹
    • Organizer
      第47回日本肝臓学会総会(モーニングセミナー)
    • Place of Presentation
      東京
    • Related Report
      2011 Annual Research Report
  • [Presentation] C型慢性肝疾患の鉄代謝異常に対するBCAA顆粒投与の有効性2011

    • Author(s)
      是永匡紹, 他
    • Organizer
      第53回日本消化器病学会大会
    • Place of Presentation
      福岡
    • Related Report
      2011 Annual Research Report
  • [Presentation] 肝炎・肝硬変と鉄に関する最近の話題2011

    • Author(s)
      是永匡紹
    • Organizer
      第15回日本肝臓学会大会(ランチョンセミナー6)
    • Place of Presentation
      福岡
    • Related Report
      2011 Annual Research Report
  • [Presentation] Dietary supplementation with branched-chain amino acids reduces hepatic iron accumulation induced by hepatitis C virus proteins and iron overload in mice2011

    • Author(s)
      Korenaga M, et al
    • Organizer
      62 the AASLD(アメリカ肝臓学会)
    • Place of Presentation
      San Francisco USA
    • Related Report
      2011 Annual Research Report
  • [Presentation] 肝内鉄過剰とミトコンドリア障害が誘導する酸化ストレスはC型肝炎ウイルス(HCV)増殖を抑制する2010

    • Author(s)
      是永匡紹, 池田正徳, 日野啓輔
    • Organizer
      第14回日本肝臓学会大会 第52回日本消化器病学会大会 パネルディスカッション7 代謝異常(金属代謝を含む)からみたC型肝炎の病態解析
    • Place of Presentation
      横浜
    • Related Report
      2012 Final Research Report
  • [Presentation] 肝内鉄過剰とミトコンドリア障害が誘導する酸化ストレスはC型肝炎ウイルス(HCV)増殖を抑制する2010

    • Author(s)
      是永匡紹, 他
    • Organizer
      第52回日本消化器病学会大会
    • Place of Presentation
      横浜
    • Related Report
      2010 Annual Research Report
  • [Presentation] Iron Induced Oxidative Stress Inhibits Viral Replication in Full Genomic Hepatitis C Virus Replicon Cells2010

    • Author(s)
      Korenaga M, 他
    • Organizer
      61 the AASLD(アメリカ肝臓学会)
    • Place of Presentation
      Boston USA
    • Related Report
      2010 Annual Research Report
  • [Book] 型慢性肝疾患の鉄代謝異常に対するBCAA顆粒投与の有効性, 酸化ストレスと肝疾患<第8巻>2012

    • Author(s)
      是永匡紹、仁科惣治、富山恭行、田中志保、是永圭子、溝上雅史、日野啓輔 坪内博仁編集
    • Publisher
      株式会社嵯峨野
    • Related Report
      2012 Final Research Report
  • [Book] 肥満・脂肪肝の栄養管理を向上させる工夫―体組成計・間接熱量計・フリーラジカル測定器を用いた試みー 酸化ストレスと肝疾患<第8巻>2012

    • Author(s)
      是永匡紹、是永圭子、鈴木淑子、寺本房子、仁科惣治、日野啓輔 坪内博仁編集
    • Publisher
      株式会社嵯峨野
    • Related Report
      2012 Final Research Report
  • [Book] 過剰鉄とミトコンドリア障害が誘導する酸化ストレスはC型肝炎ウイルス増殖を抑制する 酸化ストレスと肝疾患 第7巻2011

    • Author(s)
      是永匡紹,池田正徳,加藤宣之,日野啓輔
    • Related Report
      2012 Final Research Report

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Published: 2010-08-23   Modified: 2019-07-29  

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