title: Regulation of PKM2 and Nrf2-ARE pathway during benzoquinone induced oxidative stress in yolk sac hematopoietic stem cells.
abstract: Benzene is an occupational toxicant and an environmental pollutant that is able to induce the production of reactive oxygen species (ROS), causing oxidative stress and damages of the macromolecules in target cells, such as the hematopoietic stem cells. We had previously found that embryonic yolk sac hematopoietic stem cells (YS-HSCs) are more sensitive to benzene toxicity than the adult bone marrow hematopoietic stem cells, and that nuclear factor-erythroid-2-related factor 2 (Nrf2) is the major regulator of cytoprotective responses to oxidative stress. In the present report, we investigated the effect of PKM2 and Nrf2-ARE pathway on the cellular antioxidant response to oxidative stress induced by benzene metabolite benzoquinone (BQ) in YS-HSC isolated from embryonic yolk sac and enriched by magnetic-activated cell sorting (MACS). Treatment of the YS-HSC with various concentrations of BQ for 6 hours induces ROS generation in a dose-dependent manner. Additional tests showed that BQ is also capable of inducing expression of NADPH oxidase1 (NOX1), and several other antioxidant enzymes or drug-metabolizing enzymes, including heme oxygenase 1 (HMOX1), superoxide dismutase (SOD), catalase and NAD(P)H dehydrogenase quinone 1 (NQO1). Concomitantly, only the expression of PKM2 protein was decreased by the treatment of BQ but not the PKM2 mRNA, which suggested that BQ may induce PKM2 degradation. Pretreatment of the cells with antioxidant N-acetylcysteine (NAC) decreased ROS generation and prevented BQ-induced PKM2 degradation, suggesting involvement of ROS in the PKM2 protein degradation in cellular response to BQ. These findings suggest that BQ is a potent inducer of ROS generation and the subsequent antioxidant responses of the YS-HSC. The accumulated ROS may attenuate the expression of PKM2, a key regulator of the pyruvate metabolism and glycolysis.
authors.affiliation: School of Public Health, Wuhan University, Wuhan, Hubei, P.R. China; Hubei Key Laboratory of Allergy and Immune-related Diseases, Wuhan, Hubei, P.R. China; Hubei Biomass-resource Chemistry and Environmental Biotechnology Key Laboratory, Wuhan University, Wuhan, Hubei, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Hubei Provincial Key Laboratory for Applied Toxicology (Hubei Provincial Academy for Preventive Medicine), Wuhan, P.R. China.
authors.forename: Zhuoyue
authors.initials: Z
authors.lastname: Bi
authors.affiliation: School of Public Health, Wuhan University, Wuhan, Hubei, P.R. China; Hubei Key Laboratory of Allergy and Immune-related Diseases, Wuhan, Hubei, P.R. China; Hubei Biomass-resource Chemistry and Environmental Biotechnology Key Laboratory, Wuhan University, Wuhan, Hubei, P.R. China.
authors.forename: Tan
authors.initials: T
authors.lastname: Yang
authors.affiliation: School of Public Health, Wuhan University, Wuhan, Hubei, P.R. China; Hubei Key Laboratory of Allergy and Immune-related Diseases, Wuhan, Hubei, P.R. China; Hubei Biomass-resource Chemistry and Environmental Biotechnology Key Laboratory, Wuhan University, Wuhan, Hubei, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: School of Public Health, Wuhan University, Wuhan, Hubei, P.R. China; Hubei Key Laboratory of Allergy and Immune-related Diseases, Wuhan, Hubei, P.R. China; Hubei Biomass-resource Chemistry and Environmental Biotechnology Key Laboratory, Wuhan University, Wuhan, Hubei, P.R. China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Li
authors.affiliation: School of Public Health, Wuhan University, Wuhan, Hubei, P.R. China; Hubei Key Laboratory of Allergy and Immune-related Diseases, Wuhan, Hubei, P.R. China; Hubei Biomass-resource Chemistry and Environmental Biotechnology Key Laboratory, Wuhan University, Wuhan, Hubei, P.R. China.
authors.forename: Wenting
authors.initials: W
authors.lastname: Huang
authors.affiliation: School of Public Health, Kunming Medical University, Chenggong District, Kunming, P.R. China.
authors.forename: Liping
authors.initials: L
authors.lastname: Wang
authors.affiliation: School of Public Health, Wuhan University, Wuhan, Hubei, P.R. China; Hubei Key Laboratory of Allergy and Immune-related Diseases, Wuhan, Hubei, P.R. China; Hubei Biomass-resource Chemistry and Environmental Biotechnology Key Laboratory, Wuhan University, Wuhan, Hubei, P.R. China.
authors.forename: Shaozun
authors.initials: S
authors.lastname: Zhang
authors.affiliation: School of Public Health, Wuhan University, Wuhan, Hubei, P.R. China; Hubei Key Laboratory of Allergy and Immune-related Diseases, Wuhan, Hubei, P.R. China; Hubei Biomass-resource Chemistry and Environmental Biotechnology Key Laboratory, Wuhan University, Wuhan, Hubei, P.R. China.
authors.forename: Yanfeng
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: School of Public Health, Wuhan University, Wuhan, Hubei, P.R. China; Hubei Key Laboratory of Allergy and Immune-related Diseases, Wuhan, Hubei, P.R. China; Hubei Biomass-resource Chemistry and Environmental Biotechnology Key Laboratory, Wuhan University, Wuhan, Hubei, P.R. China.
authors.forename: Ningna
authors.initials: N
authors.lastname: Fan
authors.affiliation: School of Public Health, Wuhan University, Wuhan, Hubei, P.R. China; Hubei Key Laboratory of Allergy and Immune-related Diseases, Wuhan, Hubei, P.R. China; Hubei Biomass-resource Chemistry and Environmental Biotechnology Key Laboratory, Wuhan University, Wuhan, Hubei, P.R. China.
authors.forename: YuE
authors.initials: Y
authors.lastname: Bai
authors.affiliation: Nanchang Center for Disease Control and Prevention, Nanchang, P.R. China.
authors.forename: Wentao
authors.initials: W
authors.lastname: Song
authors.affiliation: School of Public Health, Wuhan University, Wuhan, Hubei, P.R. China; Hubei Key Laboratory of Allergy and Immune-related Diseases, Wuhan, Hubei, P.R. China; Hubei Biomass-resource Chemistry and Environmental Biotechnology Key Laboratory, Wuhan University, Wuhan, Hubei, P.R. China.
authors.forename: Chunhong
authors.initials: C
authors.lastname: Wang
authors.affiliation: School of Public Health, Wuhan University, Wuhan, Hubei, P.R. China; Hubei Key Laboratory of Allergy and Immune-related Diseases, Wuhan, Hubei, P.R. China; Hubei Biomass-resource Chemistry and Environmental Biotechnology Key Laboratory, Wuhan University, Wuhan, Hubei, P.R. China.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.affiliation: School of Public Health, Wuhan University, Wuhan, Hubei, P.R. China; Hubei Key Laboratory of Allergy and Immune-related Diseases, Wuhan, Hubei, P.R. China; Hubei Biomass-resource Chemistry and Environmental Biotechnology Key Laboratory, Wuhan University, Wuhan, Hubei, P.R. China.
authors.forename: Yongyi
authors.initials: Y
authors.lastname: Bi
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D016227:Benzoquinones / Q000494:pharmacology*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D011247:Pregnancy; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013963:Thyroid Hormones / Q000235:genetics / Q000378:metabolism*; D015017:Yolk Sac / Q000166:cytology* / Q000378:metabolism*; D000097810:Thyroid Hormone-Binding Proteins
chemical_list: D000111:Acetylcysteine; D016227:Benzoquinones; D002352:Carrier Proteins; D008565:Membrane Proteins; D051267:NF-E2-Related Factor 2; D017382:Reactive Oxygen Species; D013963:Thyroid Hormones; D000097810:Thyroid Hormone-Binding Proteins; C495636:Nfe2l2 protein, mouse; C004532:quinone