| Title | AMP-activated Protein Kinase alpha 2 Protects against Liver Injury from Metastasized Tumors via Reduced Glucose Deprivation-induced Oxidative Stress |
| Authors | Qiu, Shu-Lan Xiao, Zhi-Cheng Piao, Chun-Mei Xian, Ying-Lin Jia, Li-Xin Qi, Yong-Fen Han, Jia-Huai Zhang, You-yi Du, Jie |
| Affiliation | Capital Med Univ, Beijing Anzhen Hosp, Beijing Inst Heart Lung & Blood Vessel Dis, Minist Educ,Key Lab Remodeling Related Cardiovasc, Beijing 100029, Peoples R China. Peking Univ, Hlth Sci Ctr, Sch Basic Med Sci, Lab Cardiovasc Bioact Mol, Beijing 100191, Peoples R China. Xiamen Univ, Sch Biol Sci, Xiamen 361005, Peoples R China. Capital Med Univ, Inst Heart Lung & Blood Vessel Dis, Beijing Anzhen Hosp, Beijing 100029, Peoples R China. |
| Keywords | AMP-activated kinase (AMPK) Glucose Metastasis Oxidative Stress Tumor REACTIVE OXYGEN CELL-DEATH TNF-ALPHA SKELETAL-MUSCLE ENERGY MITOCHONDRIA PHOSPHORYLATION METABOLISM AUTOPHAGY CANCER |
| Issue Date | 2014 |
| Publisher | journal of biological chemistry |
| Citation | JOURNAL OF BIOLOGICAL CHEMISTRY.2014,289,(13),9449-9459. |
| Abstract | Background: AMPK senses energetic changes and regulates glucose metabolism. Results: AMPK 2 deficiency aggravated the glucose deprivation and necrosis of the hepatocytes via increased ROS production and decreased mitophagy. Conclusion: AMPK 2 is essential for attenuation of liver injury during tumor metastasis. Significance: This is the first time to reveal the mechanism by which glucose/energy competition induced tissue damage in tumor. It is well known that tumors damage affected tissues; however, the specific mechanism underlying such damage remains elusive. AMP-activated protein kinase (AMPK) senses energetic changes and regulates glucose metabolism. In this study, we examined the mechanisms by which AMPK promotes metabolic adaptation in the tumor-bearing liver using a murine model of colon cancer liver metastasis. Knock-out of AMPK 2 significantly enhanced tumor-induced glucose deprivation in the liver and increased the extent of liver injury and hepatocyte death. Mechanistically, we observed that AMPK 2 deficiency resulted in elevated reactive oxygen species, reduced mitophagy, and increased cell death in response to tumors or glucose deprivation in vitro. These results imply that AMPK 2 is essential for attenuation of liver injury during tumor metastasis via hepatic glucose deprivation and mitophagy-mediated inhibition of reactive oxygen species production. Therefore, AMPK 2 might represent an important therapeutic target for colon cancer metastasis-induced liver injury. |
| URI | http://hdl.handle.net/20.500.11897/389902 |
| ISSN | 0021-9258 |
| DOI | 10.1074/jbc.M113.543447 |
| Indexed | SCI(E) EI |
| Appears in Collections: | 基础医学院 |
