| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Outline of Final Research Achievements |
Activation of the mitochondrial pathway of apoptosis increased oxidative stress in hepatocytes and tBid released ROS from mitochondria. Hepatocyte-specific Bcl-xL or Mcl-1 KO mice coursed continuous hepatocyte apoptosis with increase of reciprocal regeneration, fibrosis, inflammation cytokines and oxidative stress. They also developed liver tumorgenesis. Bak, Bax or Bid deficiency attenuated hepatocytes apoptosis, oxidative stress and tumorigenesis rate in Mcl-1KO mice. An antioxidant did not affect the levels of hepatocyte apoptosis, reciprocal regeneration, fibrosis and inflammation cytokines but attenuated oxidative stress and decreased incidence rates of HCC. These results indicated that continuous hepatocyte apoptosis induced accumulation of oxidative stress in their liver which resulted in liver carcinogenesis. This study supports a concept that antioxidant therapy may be useful for suppressing liver carcinogenesis in patients with chronic liver disease.
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