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Cytoplasmic Irradiation Induces Metabolic Shift in Human Small Airway Epithelial Cells via Activation of Pim-1 Kinase

文献类型：期刊论文

作者Wu, Jinhua1,4; Zhang, Qin3; Wuu, Yen-Ruh1; Zou, Sirui1; Hei, Tom K.1,2
刊名RADIATION RESEARCH
出版日期2017-04-01
卷号187期号:4页码:441-453
DOI10.1667/RR0006CC.1
文献子类Article
英文摘要The unique cellular and molecular consequences of cytoplasmic damage caused by ionizing radiation were studied using a precision microbeam irradiator. Our results indicated that targeted cytoplasmic irradiation induced metabolic shift from an oxidative to glycolytic phenotype in human small airway epithelial cells (SAE). At 24 h postirradiation, there was an increase in the mRNA expression level of key glycolytic enzymes as well as lactate secretion in SAE cells. Using RNA-sequencing analysis to compare genes that were responsive to cytoplasmic versus nuclear irradiation, we found a glycolysis related gene, Pim-1, was significantly upregulated only in cytoplasmic irradiated SAE cells. Inhibition of Pim-1 activity using the selective pharmaceutic inhibitor Smi-4a significantly reduced the level of lactate production and glucose uptake after cytoplasmic irradiation. In addition, Pim-1 also inhibited AMPK activity, which is a well-characterized negative regulator of glycolysis. Distinct from the glycolysis induced by cytoplasmic irradiation, targeted nuclear irradiation also induced a transient and minimal increase in glycolysis that correlated with increased expression of Hif-1a. In an effort to explore the underline mechanism, we found that inhibition of mitochondria fission using the cell-permeable inhibitor mdivi-1 suppressed the induction of Pim-1, thus confirming Pim-1 upregulation as a downstream effect of mitochondrial dysfunction. Our data show and, for the first time, that cytoplasmic irradiation mediate expression level of Pim-1, which lead to glycolytic shift in SAE cells. Additionally, since glycolysis is frequently linked to cancer cell metabolism, our findings further suggest a role of cytoplasmic damage in promoting neoplastic changes. (C) 2017 by Radiation Research Society
WOS关键词CANCER-CELLS ; PROTOONCOGENE PIM-1 ; IONIZING-RADIATION ; AEROBIC GLYCOLYSIS ; NEGATIVE REGULATOR ; OXIDATIVE STRESS ; RNA-SEQ ; GROWTH ; PHOSPHORYLATES ; EXPRESSION
WOS研究方向Life Sciences & Biomedicine - Other Topics ; Biophysics ; Radiology, Nuclear Medicine & Medical Imaging
语种英语
WOS记录号WOS:000399680800006
资助机构NIH(5P01-CA49062-23 ; NIH(5P01-CA49062-23 ; NIH(5P01-CA49062-23 ; NIH(5P01-CA49062-23 ; NIH(5P01-CA49062-23 ; NIH(5P01-CA49062-23 ; NIH(5P01-CA49062-23 ; NIH(5P01-CA49062-23 ; NIH(5P01-CA49062-23 ; NIH(5P01-CA49062-23 ; NIH(5P01-CA49062-23 ; NIH(5P01-CA49062-23 ; NIH(5P01-CA49062-23 ; NIH(5P01-CA49062-23 ; NIH(5P01-CA49062-23 ; NIH(5P01-CA49062-23 ; National Natural Science Fund of China(11305204) ; National Natural Science Fund of China(11305204) ; National Natural Science Fund of China(11305204) ; National Natural Science Fund of China(11305204) ; National Natural Science Fund of China(11305204) ; National Natural Science Fund of China(11305204) ; National Natural Science Fund of China(11305204) ; National Natural Science Fund of China(11305204) ; National Natural Science Fund of China(11305204) ; National Natural Science Fund of China(11305204) ; National Natural Science Fund of China(11305204) ; National Natural Science Fund of China(11305204) ; National Natural Science Fund of China(11305204) ; National Natural Science Fund of China(11305204) ; National Natural Science Fund of China(11305204) ; National Natural Science Fund of China(11305204) ; 5R01-ES12888-09 ; 5R01-ES12888-09 ; 5R01-ES12888-09 ; 5R01-ES12888-09 ; 5R01-ES12888-09 ; 5R01-ES12888-09 ; 5R01-ES12888-09 ; 5R01-ES12888-09 ; 5R01-ES12888-09 ; 5R01-ES12888-09 ; 5R01-ES12888-09 ; 5R01-ES12888-09 ; 5R01-ES12888-09 ; 5R01-ES12888-09 ; 5R01-ES12888-09 ; 5R01-ES12888-09 ; EB-002033) ; EB-002033) ; EB-002033) ; EB-002033) ; EB-002033) ; EB-002033) ; EB-002033) ; EB-002033) ; EB-002033) ; EB-002033) ; EB-002033) ; EB-002033) ; EB-002033) ; EB-002033) ; EB-002033) ; EB-002033) ; NIH(5P01-CA49062-23 ; NIH(5P01-CA49062-23 ; NIH(5P01-CA49062-23 ; NIH(5P01-CA49062-23 ; NIH(5P01-CA49062-23 ; NIH(5P01-CA49062-23 ; NIH(5P01-CA49062-23 ; NIH(5P01-CA49062-23 ; NIH(5P01-CA49062-23 ; NIH(5P01-CA49062-23 ; NIH(5P01-CA49062-23 ; NIH(5P01-CA49062-23 ; NIH(5P01-CA49062-23 ; NIH(5P01-CA49062-23 ; NIH(5P01-CA49062-23 ; NIH(5P01-CA49062-23 ; National Natural Science Fund of China(11305204) ; National Natural Science Fund of China(11305204) ; National Natural Science Fund of China(11305204) ; National Natural Science Fund of China(11305204) ; National Natural Science Fund of China(11305204) ; National Natural Science Fund of China(11305204) ; National Natural Science Fund of China(11305204) ; National Natural Science Fund of China(11305204) ; National Natural Science Fund of China(11305204) ; National Natural Science Fund of China(11305204) ; National Natural Science Fund of China(11305204) ; National Natural Science Fund of China(11305204) ; National Natural Science Fund of China(11305204) ; National Natural Science Fund of China(11305204) ; National Natural Science Fund of China(11305204) ; National Natural Science Fund of China(11305204) ; 5R01-ES12888-09 ; 5R01-ES12888-09 ; 5R01-ES12888-09 ; 5R01-ES12888-09 ; 5R01-ES12888-09 ; 5R01-ES12888-09 ; 5R01-ES12888-09 ; 5R01-ES12888-09 ; 5R01-ES12888-09 ; 5R01-ES12888-09 ; 5R01-ES12888-09 ; 5R01-ES12888-09 ; 5R01-ES12888-09 ; 5R01-ES12888-09 ; 5R01-ES12888-09 ; 5R01-ES12888-09 ; EB-002033) ; EB-002033) ; EB-002033) ; EB-002033) ; EB-002033) ; EB-002033) ; EB-002033) ; EB-002033) ; EB-002033) ; EB-002033) ; EB-002033) ; EB-002033) ; EB-002033) ; EB-002033) ; EB-002033) ; EB-002033)
源URL[http://ir.hfcas.ac.cn:8080/handle/334002/33509]  
专题合肥物质科学研究院_中科院等离子体物理研究所
作者单位1.Columbia Univ, Coll Phys & Surg, Ctr Radiol Res, 630 West 168th St,VC 11-205, New York, NY 10032 USA
2.Columbia Univ, Mailman Sch Publ Hlth, Dept Environm Hlth Sci, New York, NY 10032 USA
3.Sichuan Univ, West China Sch Publ Hlth, Dept Environm Hlth & Occupat Med, Chengdu 610041, Sichuan, Peoples R China
4.Chinese Acad Sci, Inst Plasma Phys, Hefei 230031, Anhui, Peoples R China
推荐引用方式
GB/T 7714		 Wu, Jinhua,Zhang, Qin,Wuu, Yen-Ruh,et al. Cytoplasmic Irradiation Induces Metabolic Shift in Human Small Airway Epithelial Cells via Activation of Pim-1 Kinase[J]. RADIATION RESEARCH,2017,187(4):441-453.
APA Wu, Jinhua,Zhang, Qin,Wuu, Yen-Ruh,Zou, Sirui,&Hei, Tom K..(2017).Cytoplasmic Irradiation Induces Metabolic Shift in Human Small Airway Epithelial Cells via Activation of Pim-1 Kinase.RADIATION RESEARCH,187(4),441-453.
MLA Wu, Jinhua,et al."Cytoplasmic Irradiation Induces Metabolic Shift in Human Small Airway Epithelial Cells via Activation of Pim-1 Kinase".RADIATION RESEARCH 187.4(2017):441-453.

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来源：合肥物质科学研究院

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