2013 Fiscal Year Final Research Report
Role of autophagy in liver diseases associated with stress
| Project/Area Number |
23591000
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | University of Occupational and Environmental Health, Japan |
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Principal Investigator |
HARADA Masaru 産業医科大学, 医学部, 教授 (00241175)
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| Project Period (FY) |
2011 – 2013
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| Keywords | 肝臓学 / オートファジー / 酸化ストレス / 小胞体ストレス |
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| Research Abstract |
We investigated endoplasmic reticulum (ER) stress in hepatoma cells, and the relations between oxidative stress, autophagy and Mallory-Denk body (MDB) formation in patients with chronic hepatitis B (CHB), chronic hepatitis C (CHC) or non-alcoholic fatty liver disease (NAFLD). We treated Huh7 cells with proteasome inhibitor (PI) or free fatty acid (FFA) and evaluated ER stress, ubiquitinated proteins and LC3with western blotting. Treatment with PI or FFA increased ubiquitinated proteins and activated autophagy. Samples of CHC and NAFLD showed MDBs in areas with strong oxidative stress and that the MDB-containing cells reduced oxidative stress. Keratin 8 (K8) expression was strong in MDB-containing cells in CHC and NAFLD. Aminotransferase values were significantly lower in patients with CHC and NAFLD in whom autophagy was increased in response to oxidative stress. These results suggest that MDBs protect hepatocytes from oxidative stress and that autophagy reduces hepatic damage.
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Research Products
(45 results)
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[Journal Article] Aging modulates susceptibility to mouse liver Mallory-Denk body formation2012
Author(s)
Hanada S, Harada M, Akiba J, Abe M, Sakata M, Taniguchi E, Kawaguchi T, Koga H, Nagata E, Ueno T, Omary MB, Sata M
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Journal Title
J Histochem Cytochem
Volume: 60
Pages: 475-483
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[Journal Article] Copper incorporation into ceruloplasmin is regulated by Niemann-Pick C1 protein2011
Author(s)
Yanagimoto C, Harada M, Kumemura H, Abe M, Koga H, Sakata M, Kawaguchi T, Terada K, Hanada S, Taniguchi E, Ninomiya H, Ueno T, Sugiyama T, Sata M
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Journal Title
Hepatol Res
Volume: 41
Pages: 484-491
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[Journal Article] Late diagnosed Wilson disease with hepatic and neurological manifestations2011
Author(s)
Honma Y, Harada M, Sato M, Katsuki Y, Hiura M, Shibata M, Narita R, Harada R, Abe S, Tabaru A, Tajiri N, Simajiri S
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Journal Title
Hepatol Res
Volume: 41
Pages: 270-276
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