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Signals Induced by HCV Proteins

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HCV/Oxidative Stress and Liver Disease

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Summary

Hepatitis C virus (HCV) causes a persistent infection, chronic hepatitis, cirrhosis, and hepatocellular carcinoma. To explore the influence of HCV infection on hepatocytes, the effects of HCV proteins on intracellular signal transduction pathways, especially those related to apoptosis, fibrosis, and cell growth, were investigated. The effects of nine HCV proteins (core, NS2, NS3, NS4A, NS4B, NS5A, and NS5B) on the CRE-, SRE-, NFKB-, AP-1-, SRF-, ISRE-, HSE-, GRE-, and p53-associated pathways were investigated by use of a reporter assay. The effects of core protein on apoptosis were examined by DNA laddering and Western blotting after induction of apoptosis by Fas stimulation. The possible mechanisms of anti-apoptotic effects of core protein were investigated by RNase protection assay and a reporter assay. The effects of HCV proteins on TGF beta production were determined by a reporter assay. Among seven HCV proteins investigated, core protein had the strongest influence on intracellular signaling, especially for the SRE-, AP-1-, NFKB-, and p53-associated pathways. Core protein promoted Bc1-xL expression through the mitogen-activated protein kinase (MAPK) pathway and inhibited apoptosis. Among HCV proteins, only core protein caused TGF beta promoter activity through the MAPK pathway. From these results, core protein was considered to regulate cell growth exquisitely in hepatocytes, inhibit apoptosis, and promote liver fibrosis directly without any inflammation or the mediation of any other cells. These functions may reflect the direct action of HCV proteins on the intracellular signal transduction pathways related to chronic hepatitis pathogenesis.

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Authors and Affiliations

  1. Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan

    Motoyuki Otsuka, Naoya Kato, Hiroyoshi Taniguchi, Hideo Yoshida, Yasushi Shiratori & Masao Omata

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  1. Motoyuki Otsuka
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  2. Naoya Kato
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  3. Hiroyoshi Taniguchi
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  4. Hideo Yoshida
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  5. Yasushi Shiratori
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  6. Masao Omata
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Editors and Affiliations

  1. Department of Gastroenterology and Hepatology, Yamaguchi University School of Medicine, 1-1-1 Minami-Kogushi, 755-8505, Ube, Yamaguchi, Japan

    Kiwamu Okita M.D., Ph.D. (Professor and Chairman) (Professor and Chairman)

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© 2003 Springer Japan

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Otsuka, M., Kato, N., Taniguchi, H., Yoshida, H., Shiratori, Y., Omata, M. (2003). Signals Induced by HCV Proteins. In: Okita, K. (eds) HCV/Oxidative Stress and Liver Disease. Springer, Tokyo. https://doi.org/10.1007/978-4-431-67005-6_4

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  • DOI: https://doi.org/10.1007/978-4-431-67005-6_4

  • Publisher Name: Springer, Tokyo

  • Print ISBN: 978-4-431-67007-0

  • Online ISBN: 978-4-431-67005-6

  • eBook Packages: Springer Book Archive

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