Continuous hepatocyte apoptosis induces HCC in the liver
Project/Area Number |
24590970
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Gastroenterology
|
Research Institution | Osaka University |
Principal Investigator |
HIKITA Hayato 大阪大学, 医学(系)研究科(研究院), 特任助教(常勤) (20623044)
|
Co-Investigator(Kenkyū-buntansha) |
TATSUMI Tomohide 大阪大学, 大学院医学系研究科, 助教 (20397699)
|
Project Period (FY) |
2012-04-01 – 2015-03-31
|
Project Status |
Completed (Fiscal Year 2014)
|
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)
|
Keywords | 肝細胞死 / 肝細胞癌 / 酸化ストレス |
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.
|
Report
(4 results)
Research Products
(20 results)
-
[Journal Article] The Bcl-2 homology 3 (BH3)-only proteins Bim and Bid are functionally active and restrained by anti-apoptotic B-cell CLL/lymphoma 2 (Bcl-2) family proteins in healthy liver.2013
Author(s)
[1] Kodama T, Hikita H, Kawaguchi T, Saito Y, Tanaka S, Shigekawa M, Shimizu S, Li W, Miyagi T, Kanto T, Hiramatsu N, Tatsumi T, Takehara T.
-
Journal Title
J. Biol. Chem.
Volume: 288
Issue: 42
Pages: 30009-30018
DOI
Related Report
Peer Reviewed
-
-
-
-
-
-
-
[Presentation] Oxidative stress induced by continuous hepatocyte apoptosis drives liver carcinogenesis independently of regeneration and DNA methylation status.2013
Author(s)
Hayato Hikita, Tomohide Tatsumi, Yoshinobu Saito, Satoshi Tanaka, Satoshi Shimizu, Wei Li, Ryotaro Sakamori, Takuya Miyagi, Naoki Hiramatsu, Tetsuo Takehara.
Organizer
The 64th Annual Meeting of the American Association for the study of Liver Disease.
Place of Presentation
Washington, USA
Related Report
-
-
[Presentation] Continuous apoptosis in hepatocytes induces oxidative stress and leads to liver carcinogenesis.2013
Author(s)
Hayato Hikita, Tomohide Tatsumi, Tasuku Nakabori, Yoshinobu Saito, Tsukasa Kawaguchi, Satoshi Tanaka, Satoshi Shimizu, Ryotaro Sakamori, Takuya Miyagi, Tetsuo Takehara.
Organizer
The 17th International Symposium on Cell of the Hepatic Sinusoid.
Place of Presentation
Osaka, Japan
Related Report
-
-
-
-
[Presentation] Antioxidant has a therapeutic potential for HCC driven by chronic liver injury.2013
Author(s)
Hikita H, Tanaka S, Saito Y, Kawaguchi T, Shimizu S, Shigekawa M, Kodama T, Li W, Sakamori R, Miyagi T, Kanto T, Hiramatsu N, Tatsumi T, Takehara T
Organizer
The 2nd JSGE International Topic Conference.
Place of Presentation
Kagoshima
Related Report
-
[Presentation] Oxidative stresses play a major role in cancer development in apoptosis-prone liver.2012
Author(s)
Hayato Hikita, Takahiro Kodama, Satoshi Tanaka, Yoshinobu Saito, Satoshi Shimizu, Minoru Shigekawa, Wei Li, Takuya Miyagi, Tatsuya Kanto, Naoki Hiramatsu, Tomohide Tatsumi,Tetsuo Takehara.
Organizer
The 63rd Annual Meeting of the American Association for the study of Liver Disease.
Place of Presentation
Boston, USA
Related Report
-
-
[Presentation] Oxidative stresses play a major role in cancer development in apoptosis-prone liver.2012
Author(s)
Hayato Hikita, Takahiro Kodama, Satoshi Tanaka, Yoshinobu Saito, Satoshi Shimizu, Minoru Shigekawa, Wei Li, Takuya Miyagi, Tatsuya Kanto, Naoki Hiramatsu, Tomohide Tatsumi,Tetsuo Takehara.
Organizer
第71回日本癌学会学術総会
Place of Presentation
札幌
Related Report
-
-
-