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Clarifying the molecular mechanism of the Nrf-2 activator carnosic acid in the regulation of the hepatocyte apoptosis

Research Project

Project/Area Number 24590992
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Gastroenterology
Research InstitutionIwate Medical University

Principal Investigator

WANG TING  岩手医科大学, 医学部, 助教 (70416171)

Co-Investigator(Renkei-kenkyūsha) TAKIKAWA Yasuhiro  岩手医科大学医学部, 消化器・肝臓内科肝臓分野, 教授 (50254751)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Keywordsカルノシン酸 / シグナル / アポトーシス / 酸化ストレス / 細胞死 / Carnosic acid / Nrf2 / Oxidative stress
Outline of Final Research Achievements

Carnosic acid (CA) did not induce the activity of Nrf2 anti-oxidative system in vivo. CA at concentrations as low as 1μM significantly protected against H2O2-induced cytotoxicity and apoptosis of hepatocytes. H2O2 induced phosphorylation of extracellular-signal-regulated kinase 1 and 2 (ERK1/2) in primary hepatocytes. U0126 inhibited the decrease in cell viability induced by H2O2. Co-treatment with CA inhibited ERK1/2 activation induced by H2O2. 4. CA at 1 μM increased protein levels of SIRT1. Pretreatment with EX527 or transfection of SiRNA of SIRT1 weakened the protective effects of CA against H2O2-induced cell death. Our data indicate that CA protects against oxidative stress-induced cytotoxicity via SIRT1 by regulating subsequent downstream factors such as ERK1/2. On the other hand, CA decreased cell viability of human hepatoma Huh 7 and HepG2 cell line in a cell-dependent way. SIRT1/Nrf2 signaling is involved in its function.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (10 results)

All 2014 2013 2012

All Journal Article (6 results) (of which Peer Reviewed: 6 results,  Open Access: 2 results,  Acknowledgement Compliant: 2 results) Presentation (4 results)

  • [Journal Article] Proliferation of mouse liver stem/progenitor cells induced by plasma from2014

    • Author(s)
      Wang T, Takikawa Y, Watanabe A, Kakisaka K, Oigawa K, Miyamoto Y, Suzuki K.
    • Journal Title

      J Gastroenterol.

      Volume: 49 Issue: 12 Pages: 1557-1566

    • DOI

      10.1007/s00535-013-0927-6

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Usefulness and accuracy of the international normalized ratio and activity percent of prothrombin time in patients with liver disease.2014

    • Author(s)
      Takikawa Y, Harada M, Wang T, Suzuki K.
    • Journal Title

      Hepatol Res.

      Volume: 44 Issue: 1 Pages: 92-101

    • DOI

      10.1111/hepr.12093

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Proliferation of mouse liver stem/progenitor cells induced by plasma from patients with acute liver failure is modulated by P2Y2 receptor-mediated JNK activation.2013

    • Author(s)
      Wang T, Takikawa Y, Watanabe A, Kakisaka K, Oikawa K, Miyamoto Y, Suzuki K.
    • Journal Title

      J Gastroenterol.

      Volume: Epub ahead of print

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Evodiamine Inhibits Insulin-Stimulated mTOR-S6K Activation and IRS1 Serine Phosphorylation in Adipocytes and Improves Glucose Tolerance in Obese/Diabetic Mice.2013

    • Author(s)
      Wang T, Kusudo T, Takeuchi T, Yamashita Y, Kontani Y, Okamatsu Y, Saito M, Mori N, Yamashita H.
    • Journal Title

      PLoS One.

      Volume: 8

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Carnosic acid prevents lipid accumulation in hepatocytes through EGF/MAPK pathway2012

    • Author(s)
      Wang T, Takikawa Y, Tabuchi T, Kosaka K, Satoh T, Suzuki K. .
    • Journal Title

      J Gastroenterol

      Volume: 47 Pages: 805-13

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Negative regulation of human astrocytes by Interferon (IFN) α in relation to growth inhibition and impaired glucose utilization.2012

    • Author(s)
      Wang T, TakikawaY, Sawara K, YoshidaY, Suzuki K.
    • Journal Title

      Neurochem Res

      Volume: 37 Pages: 1898-905

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] Lysosome dysfunction contributes impairment of autophagy in mouse model of liver steatosis.2014

    • Author(s)
      A. Suzuki, K. Kakisaka, A. Watanabe, T. Wang, Y. Takikawa
    • Organizer
      AASLD
    • Place of Presentation
      Boston
    • Year and Date
      2014-11-07 – 2014-11-11
    • Related Report
      2014 Annual Research Report
  • [Presentation] Carnosic acid protects against oxidative stress-induced cytotoxicity in primary hepatocytes, induces tumor cell death, and inhibits TGFβ-induced migration and invasion in HepG2 cells.2013

    • Author(s)
      Takikawa Y、Wang T, Watanabe A, Kakisaka K, Onodera M, Oikawa K.
    • Organizer
      AASLD
    • Place of Presentation
      Washington DC.
    • Related Report
      2013 Research-status Report
  • [Presentation] IFN-α/5-FU併用によるTGFβシグナルへの影響2013

    • Author(s)
      王挺、滝川康裕、葛西和博、渡辺亜沙子、鈴木一幸。
    • Organizer
      第49回肝臓学会総会
    • Place of Presentation
      東京
    • Related Report
      2012 Research-status Report
  • [Presentation] IFN-α/5-FU併用によるTGFβの発現量および分泌量変化への影響2012

    • Author(s)
      王挺
    • Organizer
      JDDW 2012
    • Place of Presentation
      神戸
    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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