title: Activation of NRF2 pathway in spleen, thymus as well as peripheral blood mononuclear cells by acute arsenic exposure in mice.
abstract: Arsenic has already been demonstrated to activate the nuclear factor erythroid 2-related factor 2 (NRF2) in many different organs and cell lines. The present study tried to explore the expression of NRF2 pathway by acute arsenic exposure in immune system in vivo. Our results showed that treatment with arsenic (sodium arsenite, 5, 10 and 20mg/kg, intra-gastrically) increased the expression of NRF2 and its downstream targets heme oxygenase-1 (HO-1), glutathione-S-transferase (GST), glutamate-cysteine ligase (GCL) and glutathione reductase (GR) consistently in spleen, thymus, as well as peripheral blood mononuclear cells (PBMCs), as early as treatment from 6h. Arsenic was also detected to up-regulate the mRNA levels of Hmox1, NAD(P)H: quinine oxidoreductase 1 (Nqo1), Gclc and Gclm in spleen and thymus. Besides, we detected the enhancement of Kelch-like ECH-associated protein (KEAP1) expression in these immune organs and immunocytes. What's more, our results also found the imbalanced oxidative redox status under the circumstances that arsenic activated NRF2 pathway, reflected by the generation of lipid peroxidation, as well as the reduction of antioxidative capacities in both spleen and thymus. Taken together, our results here strongly suggested the expression and activation of NRF2 pathway by acute arsenic exposure in immune system in vivo. Further studies are being investigated to explore the possible roles and functions of NRF2 pathway stimulation in the regulation of immune responses of this metalloid.
authors.affiliation: Department of Occupational and Environmental Health, Key Laboratory of Arsenic-related Biological Effects and Prevention and Treatment in Liaoning Province, School of Public Health, China Medical University, Shenyang 110013, China.
authors.forename: Xiaoxu
authors.initials: X
authors.lastname: Duan
authors.affiliation: Department of Occupational and Environmental Health, Key Laboratory of Arsenic-related Biological Effects and Prevention and Treatment in Liaoning Province, School of Public Health, China Medical University, Shenyang 110013, China.
authors.forename: Jinlong
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Occupational and Environmental Health, Key Laboratory of Arsenic-related Biological Effects and Prevention and Treatment in Liaoning Province, School of Public Health, China Medical University, Shenyang 110013, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Occupational and Environmental Health, Key Laboratory of Arsenic-related Biological Effects and Prevention and Treatment in Liaoning Province, School of Public Health, China Medical University, Shenyang 110013, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Occupational and Environmental Health, Key Laboratory of Arsenic-related Biological Effects and Prevention and Treatment in Liaoning Province, School of Public Health, China Medical University, Shenyang 110013, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Occupational and Environmental Health, Key Laboratory of Arsenic-related Biological Effects and Prevention and Treatment in Liaoning Province, School of Public Health, China Medical University, Shenyang 110013, China.
authors.forename: Huifang
authors.initials: H
authors.lastname: Nie
authors.affiliation: Environment and Non-Communicable Diseases Research Center, School of Public Health, China Medical University, Shenyang 110013, China.
authors.forename: Guifan
authors.initials: G
authors.lastname: Sun
authors.affiliation: Department of Occupational and Environmental Health, Key Laboratory of Arsenic-related Biological Effects and Prevention and Treatment in Liaoning Province, School of Public Health, China Medical University, Shenyang 110013, China. Electronic address: libing@mail.cmu.edu.cn.
authors.forename: Bing
authors.initials: B
authors.lastname: Li
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001151:Arsenic / Q000008:administration & dosage* / Q000633:toxicity; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D004781:Environmental Exposure / Q000009:adverse effects; D005260:Female; D015386:Hazardous Substances / Q000008:administration & dosage* / Q000633:toxicity; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D000072019:Kelch-Like ECH-Associated Protein 1; D007963:Leukocytes, Mononuclear / Q000276:immunology; D015227:Lipid Peroxidation; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D010084:Oxidation-Reduction; D015398:Signal Transduction; D013154:Spleen / Q000502:physiology*; D013950:Thymus Gland / Q000502:physiology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; D015386:Hazardous Substances; C117301:Keap1 protein, mouse; D000072019:Kelch-Like ECH-Associated Protein 1; D008565:Membrane Proteins; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; D016660:NAD(P)H Dehydrogenase (Quinone); C491732:Nqo1 protein, mouse; D001151:Arsenic
keywords: Arsenic; Immune; NRF2; Peripheral blood mononuclear cells; Spleen; Thymus