| Project/Area Number |
09253102
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Research Institution | Institute for Virus Research, Kyoto University |
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Principal Investigator |
SHIMOTOHNO Kunitada Kyoto University Institute for Virus Research, Professor, ウイルス研究所, 教授 (10000259)
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| Co-Investigator(Kenkyū-buntansha) |
KANEKO Shuichi Medical School of Kanazawa University, Associate Professor, 医学部, 助教授 (60185923)
MURAKAMI Seishi Cancer Institute, Kanazawa University, Professor, がん研究所, 教授 (90019878)
KOIKE Katsurou Medical School of the Tokyo University, Associate Professor, 癌研究所・遺伝子研究施設部, 部長 (30085625)
HAYASHI Norio Medical School of Osaka University, Professor, 医学部, 教授 (00144478)
KOHARA Michinori Tokyo Metropolitan Institute of Medical Sciences, Section Head, 放射線研究部, 室長 (10250218)
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| Project Period (FY) |
1998 – 1999
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| Keywords | hepatitis C virus / hepatitis B virus / apoptosis / NFkB siganling / HBx protein / mitochondria / inflammation / caspase activity |
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| Research Abstract |
(l) HBV X protein has versatile functions. One of such the functions is to modulate cellular transcriptional machinary. It was shown that X protein associates with one of RNA polymerase binding protein and that X protein also competes with other cellular protein to interact with transcriptional machinary.
(2) HBV X protein associates with mitochondrial membrane and disrupt the function of it. This disruption induces apoptosis. (3) HCV encode several proteins, some of which are shown to modulate cell proliferation. Among them we found that HCV core protein has anti-apoptotic function to cells induced by anti-Fas antibody or TNFa.
(4) HCV protein also functions to activate Raf/Ras signaling by yet unclarified mechanism.
(5) Trangenic mice expressing the entire HCV proteins was analyzed for their activation of CTL to clarify the mechanism of persistence of survival of HCV protein expressing hepatocytes. It was shown from this analysis that the level of MHC class II molecule on cell surface of dendritic cells was reduced although the production of the protein was not altered. Thus, it is suggested that activation of CTL by the antigen presenting cells is down regulated in this mouse and this may be one mechanism that the CTL activity in patients with chronic hepatitis is low.
(6) Cancerous tissues of hepatocyte often have anti-apoptotic activity. To clarify the mechanism underling this phenomenon, phosphorylation of BAD, a regulator of apoptosis, was examined. Phosphorylation of BAD was enhanced in the cancerous portion, suggesting that BAD play a role in anti-apoptotic function of hepatoma cells.
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