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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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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