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Selenium Prevents Lead-Induced Necroptosis by Restoring Antioxidant Functions and Blocking MAPK/NF-κB Pathway in Chicken Lymphocytes

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Abstract

Recent studies have identified a new existence of a genetically programmed and regulated cell death characterized by necrotic cell death morphology, termed necroptosis. Lead (Pb) is a ubiquitously distributed environmental pollutant that is highly toxic to animals and human beings. However, no detailed report has been conducted on the necroptosis in lymphocytes caused by Pb. Selenium (Se), a trace element in the body, has been shown to exert cytoprotective effect in numerous pathological injury caused by heavy metals. Here, lymphocytes isolated from chicken spleen were divided into four groups, control group, Se group, Pb group, and Pb + Se co-treatment group to investigate the potential mechanism in the necroptosis triggered by Pb and in the antagonistic effect of Se on Pb toxicity. Flow cytometry analysis and AO/EB staining showed Pb caused typical necrosis characteristics in the lymphocytes. The expression of RIP1, RIP3, and MLKL was increased, whereas the level of caspase 8 was declined in Pb group, which proved the occurrence of necroptosis. Meanwhile, Pb exposure disrupted the antioxidant enzyme (SOD, GSH-Px, and CAT) balance, promoted the expression of MAPK/NF-κB pathway factors (ERK, JNK, p38, NF-κB, and TNF-α), and activated HSPs (HSP27, HSP40, HSP60, HSP70, and HSP90). However, those Pb-induced changes were significantly alleviated in Se + Pb group. Our study revealed that Pb could trigger lymphocyte necroptosis through MAPK/NF-κB pathway activated by oxidative stress and that Se could antagonize Pb-induced necroptosis in chicken lymphocytes.

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Funding

The research was supported by funds provided by the China Agriculture Research System-41-17 and the National Key Research and Development Program of China (No. 2016YFD0500501).

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  1. Jiayong Zhang, Xiaofang Hao and Shiwen Xu contributed equally to this work.

Authors and Affiliations

  1. College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, People’s Republic of China

    Jiayong Zhang & Shiwen Xu

  2. Animal Disease Control and Prevention of Heilongjiang Province, No. 243 Haping Road, Xiangfang District, Harbin, 150069, China

    Jiayong Zhang & Xiaofang Hao

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  1. Jiayong Zhang
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Shiwen Xu and Gang Sun conceived of and designed the experiments. Jiayong Zhang and Xiaofang Hao performed the experiments. Jiayong Zhang analyzed the data and wrote the paper. Shiwen Xu assisted in critically revising the manuscript.

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Zhang, J., Hao, X. & Xu, S. Selenium Prevents Lead-Induced Necroptosis by Restoring Antioxidant Functions and Blocking MAPK/NF-κB Pathway in Chicken Lymphocytes. Biol Trace Elem Res 198, 644–653 (2020). https://doi.org/10.1007/s12011-020-02094-y

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