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Aldo-keto reductase family 1 member B10 promotes cell survival by regulating lipid synthesis and eliminating carbonyls

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成果类型:
期刊论文
作者:
Wang, Chun;Yan, Ruilan;Luo, Dixian;Watabe, Kounosuke;Liao, Duan-Fang;Cao, Deliang
通讯作者:
Cao, D.
作者机构:
[Wang, Chun] Department of Medical Microbiology, SimmonsCooper Cancer Institute, Southern Illinois University School of Medicine, Springfield, Illinois 62702, USA
通讯机构:
[Cao, Deliang] So Illinois Univ, Sch Medicine, Dept Med Microbiol Immunol & Cell Biol, SimmonsCooper Canc Inst, 913 N Rutledge St, Springfield, IL 62702 USA.
Dept. of Medical Microbiology, Immunology, and Cell Biology, Simmons Cooper Cancer Institute, Southern Illinois University School of Medicine, 913 N. Rutledge St., United States
语种:
英文
关键词:
[carbonyl - Acetyl-CoA carboxylase - Aldo-keto reductase - Apoptosis - Caspase-3 - Cell survival - Cellular lipid - End-products - Epalrestat - Fatty acid synthesis - Human colon - Lipid peroxides - Lipid synthesis - Lung Cancer - Lung carcinoma - Mitochondrial Cytochrome C - Mitochondrial function - Oxidative status - Palmitic acid - Reactive oxygen species - Small intestine - Ubiquitin
期刊:
Journal of Biological Chemistry
ISSN:
0021-9258
年:
2009
卷:
284
期:
39
页码:
26742-26748
基金类别:
National Institutes of Health [CA122327, CA122622]; American Cancer Society [RSG-04-031-01-CCE]; National Major Basic Research Program of China (973 Program) [2006CB 503808]
机构署名:
本校为其他机构
院系归属:
药学与生物科学学院
摘要:
Aldo-keto reductase family 1 member B10 (AKR1B10) is primarily expressed in the normal human colon and small intestine but overexpressed in liver and lung cancer. Our previous studies have shown that AKR1B10 mediates the ubiquitin-dependent degradation of acetyl-CoA carboxylase-α. In this study, we demonstrate that AKR1B10 is critical to cell survival. In human colon carcinoma cells (HCT-8) and lung carcinoma cells (NCIH460), small-interfering RNA-induced AKR1B10 silencing resulted in caspase-3-mediated apoptosis. In these cells, the total and subspecies of cellular lipids, particularly of phospholipids, were decreased by more than 50%, concomitant with 2 - 3-fold increase in reactive oxygen species, mitochondrial cytochrome c efflux, and caspase-3 cleavage. AKR1B10 silencing also increased the levels of α,β-unsaturated carbonyls, leading to the 2 - 3-fold increase of cellular lipid peroxides. Supplementing the HCT-8 cells with palmitic acid (80 μM), the end product of fatty acid synthesis, partially rescued the apoptosis induced by AKR1B10 silencing, whereas exposing the HCT-8 cells to epalrestat, an AKR1B10 inhibitor, led to more than 2-fold elevation of the intracellular lipid peroxides, resulting in apoptosis. These data suggest that AKR1B10 affects cell survival through modulating lipid synthesis, mitochondrial function, and oxidative status, as well as carbonyl levels, being an important cell survival protein. ©2009 by The American Society for Biochemistry and Molecular Biology, Inc.

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