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学科主题: 基础医学
题名:
AMP-activated Protein Kinase alpha 2 Protects against Liver Injury from Metastasized Tumors via Reduced Glucose Deprivation-induced Oxidative Stress
作者: 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
发表日期: 2014-03-28
DOI: 10.1074/jbc.M113.543447
卷: 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
所属项目编号: 2009CB522205 ; 2012AA02A201 ; 81230006 ; 31090363 ; 81000871
项目资助者: Chinese Ministry of Science and Technology ; National Natural Science Foundation of China
WOS记录号: WOS:000333472100060
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内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/54859
Appears in Collections:基础医学院_期刊论文

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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

Recommended Citation:
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.
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