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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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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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 / 肝疾患 / Mallory-Denk体 / ウイルソン病 / 非アルコール性脂肪性肝疾患 / 脂肪性肝疾患 / ウイルス性肝炎 |
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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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Report
(4 results)
Research Products
(89 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
Related Report
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[Journal Article] Aging modulates susceptibility to mouse liver Mallory-Denk body formation.2012
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
Issue: 6
Pages: 475-483
DOI
Related Report
Peer Reviewed
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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
NAID
Related Report
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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
Related Report
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