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Cellular proteomic profiling of esophageal epithelial cells cultured under physioxia or normoxia reveals high correlation of radiation response

查看全文 作　　者：Hui [1]Luo;Yanan [1]Sun;Liuxiang [2]Wang;Ran [3]Zhao;Beggs [3,4]James 高影响力作者 机构地区：[1]Department of Radiation Oncology,Affiliated Cancer Hospital of Zhengzhou University,Zhengzhou 450008,China;[2]Academic of Medical Science,Zhengzhou University,Zhengzhou 450001,China;[3]China-US(Henan)Hormel Cancer Institute,Zhengzhou 450003,China;[4]University of Warwick,UK高影响力机构 出　　处：《Radiation Medicine and Protection》索引2023年第4卷第2期,共7页高影响力期刊 基　　金：supported by the Medical Science and Technology Research Program of Henan province (No. LHGJ20210171);Bethune Cancer Radiotherapy Translational Medicine Research Program (No. flzh202115), China. 摘　　要：Objective To investigate the radiation response and proteomic profiling of esophageal epithelial cells cultured under physioxia and normoxia.Methods The human immortalized normal esophageal epithelial cell line SHEE cells were cultured under normoxia(21%)and physioxia(4%),respectively.A clonogenic assay was performed to evaluate the radiation response of SHEE cells.Cellular proteomic profiling of SHEE cells maintained under physioxia and normoxia was conducted to determine the differentially expressed proteins.Then,the identified differentially expressed proteins were validated by Western blot.Results SHEE cells exposed to normoxia showed an increased radiation response compared to physioxia(irradiation dose≥10Gy,P<0.05).Over 1200 non-redundant proteins were identified in the collected samples.Protein expression was compared between physioxia and normoxia,42 proteins were downregulated and 45 proteins upregulated,in which oxidative phosphorylation was the most significantly enriched pathway.When cells were cultured under normoxia conditions,the induction of antioxidant genes appeared to contribute to form a phenotype adapted to the environment with high oxygen-content.Further analysis validated NRF2,BIP,VCP,SOD1,and YAP1 were the key regulators of this phenotype.Conclusions Compared with physioxia,normoxic cell culture condition can enhance the radiation response.This study could stimulate in vivo microenvironment,and provide a basis for radiation-induced normal tissue damage. 关 键 词：Esophageal epithelial cell Radiation response PROTEOMICS NORMOXIA Physioxia
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