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学科主题基础医学
AMP-activated Protein Kinase alpha 2 Protects against Liver Injury from Metastasized Tumors via Reduced Glucose Deprivation-induced Oxidative Stress
Qiu, Shu-Lan1; Xiao, Zhi-Cheng1; Piao, Chun-Mei1; Xian, Ying-Lin1; Jia, Li-Xin1; Qi, Yong-Fen2; Han, Jia-Huai3; Zhang, You-yi2; Du, Jie1
关键词Amp-activated Kinase (Ampk) Glucose Metastasis Oxidative Stress Tumor
刊名JOURNAL OF BIOLOGICAL CHEMISTRY
2014-03-28
DOI10.1074/jbc.M113.543447
289期:13页:9449-9459
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Biochemistry & Molecular Biology
研究领域[WOS]Biochemistry & Molecular Biology
关键词[WOS]REACTIVE OXYGEN ; CELL-DEATH ; TNF-ALPHA ; SKELETAL-MUSCLE ; ENERGY ; MITOCHONDRIA ; PHOSPHORYLATION ; METABOLISM ; AUTOPHAGY ; CANCER
英文摘要

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.

语种英语
WOS记录号WOS:000333472100060
项目编号2009CB522205 ; 2012AA02A201 ; 81230006 ; 31090363 ; 81000871
资助机构Chinese Ministry of Science and Technology ; National Natural Science Foundation of China
引用统计
被引频次:7[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/54859
专题北京大学基础医学院
作者单位1.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
2.Xiamen Univ, Sch Biol Sci, Xiamen 361005, Peoples R China
3.Peking Univ, Hlth Sci Ctr, Sch Basic Med Sci, Lab Cardiovasc Bioact Mol, Beijing 100191, Peoples R China
推荐引用方式
GB/T 7714
Qiu, Shu-Lan,Xiao, Zhi-Cheng,Piao, Chun-Mei,et al. AMP-activated Protein Kinase alpha 2 Protects against Liver Injury from Metastasized Tumors via Reduced Glucose Deprivation-induced Oxidative Stress[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2014,289(13):9449-9459.
APA Qiu, Shu-Lan.,Xiao, Zhi-Cheng.,Piao, Chun-Mei.,Xian, Ying-Lin.,Jia, Li-Xin.,...&Du, Jie.(2014).AMP-activated Protein Kinase alpha 2 Protects against Liver Injury from Metastasized Tumors via Reduced Glucose Deprivation-induced Oxidative Stress.JOURNAL OF BIOLOGICAL CHEMISTRY,289(13),9449-9459.
MLA Qiu, Shu-Lan,et al."AMP-activated Protein Kinase alpha 2 Protects against Liver Injury from Metastasized Tumors via Reduced Glucose Deprivation-induced Oxidative Stress".JOURNAL OF BIOLOGICAL CHEMISTRY 289.13(2014):9449-9459.
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