College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, People's Republic of China.
Animal Disease Control and Prevention of Heilongjiang Province, No. 243 Haping Road, Xiangfang District, Harbin, 150069, China.
Biol Trace Elem Res. 2020 Dec;198(2):644-653. doi: 10.1007/s12011-020-02094-y. Epub 2020 Apr 12.
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.
最近的研究发现了一种新的细胞程序性死亡方式，即受基因调控的细胞死亡，其形态学特征为坏死性细胞死亡，被称为坏死性细胞凋亡。铅（Pb）是一种广泛分布于环境中的污染物，对动物和人类具有高度毒性。然而，目前尚未有关于 Pb 引起淋巴细胞坏死性细胞凋亡的详细报道。硒（Se）是人体中的一种微量元素，已被证明在许多由重金属引起的病理损伤中具有细胞保护作用。在这里，我们将鸡脾脏分离的淋巴细胞分为对照组、Se 组、Pb 组和 Pb+Se 共处理组，以研究 Pb 引发的细胞坏死和 Se 拮抗 Pb 毒性的潜在机制。流式细胞术分析和 AO/EB 染色显示 Pb 导致淋巴细胞呈现典型的坏死特征。Pb 组中 RIP1、RIP3 和 MLKL 的表达增加，而 caspase 8 的水平下降，证明发生了坏死性细胞凋亡。同时，Pb 暴露破坏了抗氧化酶（SOD、GSH-Px 和 CAT）平衡，促进了 MAPK/NF-κB 通路因子（ERK、JNK、p38、NF-κB 和 TNF-α）的表达，并激活了 HSPs（HSP27、HSP40、HSP60、HSP70 和 HSP90）。然而，在 Se+Pb 组中，这些 Pb 诱导的变化明显减轻。我们的研究表明，Pb 可以通过氧化应激激活的 MAPK/NF-κB 通路引发淋巴细胞坏死性细胞凋亡，而 Se 可以拮抗 Pb 诱导的鸡淋巴细胞坏死性细胞凋亡。
