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

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.

journal_name

Biol Trace Elem Res

authors

Zhang J,Hao X,Xu S

doi

10.1007/s12011-020-02094-y

subject

Has Abstract

pub_date

2020-12-01 00:00:00

pages

644-653

issue

2

eissn

0163-4984

issn

1559-0720

pii

10.1007/s12011-020-02094-y

journal_volume

198

pub_type

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