Study on molecular mechanisms of glucose metabolic disorders mediated by hepatitis C virus
Project/Area Number |
24590976
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Gastroenterology
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Research Institution | Kobe University |
Principal Investigator |
HOTTA Hak 神戸大学, 医学(系)研究科(研究院), 教授 (40116249)
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Co-Investigator(Kenkyū-buntansha) |
SHOJI Ikuo 神戸大学, 大学院医学研究科, 准教授 (40356241)
DENG Lin 神戸大学, 大学院医学研究科, 助教 (40437497)
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Project Period (FY) |
2012-04-01 – 2015-03-31
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Project Status |
Completed (Fiscal Year 2014)
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Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
|
Keywords | C型肝炎ウイルス / 感染症 / 糖新生 / Fox01 / 脱リン酸化 / MKP3 / アポトーシス / Bim / C型肝炎ウイルス / FoxO1 |
Outline of Final Research Achievements |
The purpose of this study was to elucidate the molecular mechanism(s) of HCV-mediated activation of the transcription factor FoxO1 that is associated with increased gluconeogenesis and induction of apoptosis through oxidative stress and JNK activation. The results obtained demonstrated that HCV infection induces oxidative stress (production of reactive oxygen species [ROS]) and JNK activation, which leads to increased expression of the phosphatase MKP3 to mediate dephosphorylation (activation) and nuclear localization of FoxO1, thereby promoting gluconeogenesis. Also, HCV-induced oxidative stress and JNK activation lead to increased expression of the pro-apoptotic protein Bim and activation of another pro-apoptotic protein Bax, thereby triggering mitochondrion-mediated apoptosis.
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Report
(4 results)
Research Products
(73 results)
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[Journal Article] Analysis of interleukin-28B polymorphisms and pegylated-interferon/ribavirin response of Indonesian chronic hepatitis C2014
Author(s)
Juniastuti, Wibowo BP, Wibawa IDN, Utsumi T, Mustika S, Amin M, Wahyuni RM, Kurniawan H, Hendrayana A, Setiawan PB, Yamani LN, Soetjipto, Yano Y, Hotta H, Hayashi Y, Lusida MI.
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Journal Title
J Clin Microbiol
Volume: in press
Issue: 6
Pages: 2193-5
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Mutational diversity of NS5A and NS3 during triple therapy (telaprevir, pegylated-interferon-α 2b and ribavirin) for genotype 1b chronic hepatitis C2014
Author(s)
Bai F, Yano Y, Kim SR, Seo Y, Miki A, Saito M, Hirano H, Momose K, Minami A, Hatazawa Y, Hayakumo T, Widasari DI, Rinonce HT, Sugano M, Tani S, Yoon S, Imoto S, Azuma T, Hotta H, Hayashi Y
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Journal Title
Int J Mol Med
Volume: in press
Issue: 6
Pages: 1652-1656
DOI
Related Report
Peer Reviewed
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[Journal Article] Antiviral activity of extracts from Morinda citrifolia leaves and chlorophyll catabolites, pheophorbide a and pyropheophorbide a, against hepatitis C virus.2014
Author(s)
Ratnoglik SL, Aoki C, Sudarmono P, Komoto M, Deng L, Shoji I, Fuchino H, Kawahara N, Hotta H.
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Journal Title
Microbiology and Immunology
Volume: 58
Issue: 3
Pages: 188-194
DOI
Related Report
Peer Reviewed
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[Journal Article] Anti-hepatitis C virus compounds obtained from Glycyrrhiza uralensis and other Glycyrrhiza species2014
Author(s)
Adianti M, Aoki C, Komoto M, Deng L, Shoji I, Wahyuni TS, Lusida MI, Soetjipto, Fuchino H, Kawahara N, Hotta H
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Journal Title
Microbiol Immunol
Volume: 58(3)
Issue: 3
Pages: 180-7
DOI
Related Report
Peer Reviewed
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[Journal Article] High rate of seronegative HCV infection in HIV-positive patients2014
Author(s)
Juniastuti, Utsumi T, Nasronudin, Alimsardjono L, Amin M, Adianti M, Yano Y, Soetjipto, Hayashi Y, Hotta H, Lusida MI
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Journal Title
Biomed Rep
Volume: 2(1)
Issue: 1
Pages: 79-84
DOI
Related Report
Peer Reviewed
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[Journal Article] Antiviral activities of Indonesian medicinal plants in the East Java region against hepatitis C virus.2013
Author(s)
Wahyuni TS, Tumewu L, Permanasari AA, Apriani E, Adianti M, Rahman A, Widyawaruyanti A, Lusida MI, Fuad A, Soetjipto D, Nasronudin D, Fuchino H, Kawahara N, Shoji I, Deng L, Aoki C, Hotta H.
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Journal Title
Virology Journal
Volume: 10
Issue: 1
Pages: 259-259
DOI
NAID
Related Report
Peer Reviewed
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[Journal Article] Factors of response to pegylated interferon/ribavirin combination therapy and mechanism of viral clearance2013
Author(s)
Sugimoto K, Kim SR, El-Shamy A, Imoto S, Ando K, Kim KI, Tanaka Y, Yano Y, Kim SK, Hasegawa Y, Fujinami A, Ohta M, Takashi H, Hotta H, Hayashi Y, Kudo M
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Journal Title
Dig Dis
Volume: 31(5-6)
Issue: 5-6
Pages: 421-425
DOI
Related Report
Peer Reviewed
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[Journal Article] Prediction of response to pegylated interferon/ribavirin combination therapy for chronic hepatitis C genotypes 2a and 2b and high viral load.2013
Author(s)
Kim SR, El-Shamy A, Imoto S, Kim KI, Sugimoto K, Kim SK, Tanaka Y, Hatae T, Hasegawa Y, Fujinami A, Ohta M, Hotta H, Kudo M
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Journal Title
Dig Dis
Volume: 31(5-6)
Issue: 5-6
Pages: 426-433
DOI
Related Report
Peer Reviewed
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[Journal Article] Outcome of double-filtration plasmapheresis plus interferon treatment in nonresponders to pegylated interferon plus ribavirin combination therapy2013
Author(s)
Sugimoto K, Kim SR, El-Shamy A, Imoto S, Fujioka H, Kim KI, Tanaka Y, Yano Y, Kim SK, Hasegawa Y, Fujinami A, Ohta M, Hatae T, Hotta H, Hayashi Y, Kudo M
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Journal Title
Dig Dis
Volume: 31(5-6)
Issue: 5-6
Pages: 434-439
DOI
Related Report
Peer Reviewed
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[Presentation] Chalepin and pseudane IX isolated from Ruta angustifolia leaves inhibit hepatitis C virus replication.2014
Author(s)
Wahyuni T S, Widyawaruyanti A, Lusida M I, Fuad A, Soetjipto, Fuchino H, Kawahara N, Hayashi Y, Aoki C, Hotta H
Organizer
The 13th Awaji International Forum on Infection and Immunity in Nara.
Place of Presentation
Nara, Japan
Year and Date
2014-09-23 – 2014-09-26
Related Report
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[Presentation] Antiviral activity of chlorophyll derivatives, pheophorbide a, chlorin e6 and mono-L-aspartyl chlorin e6 (NPe6), against hepatitis C virus2013
Author(s)
Hak Hotta, Chie Aoki, Suratno Lulut Ratnoglik, Pratiwi Sudarmono, Mari Komoto, Lin Deng, Ikuo Shoji, Hiroyuki Fuchino, Nobuo Kawahara
Organizer
20th International Symposium on Hepatitis C Virus and Related Viruses
Place of Presentation
Melbourne, Australia
Related Report
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