College of Animal Science, Anhui Science and Technology University, Fengyang, 233100, Anhui, China.
Anhui Province Key Laboratory of Animal Nutritional Regulation and Health, Anhui Science and Technology University, Fengyang, 233100, Anhui, China.
Biometals. 2022 Aug;35(4):699-710. doi: 10.1007/s10534-022-00394-5. Epub 2022 May 5.
Zearalenone (ZEL)-induced apoptosis in different cells is mediated by various molecular mechanisms, including endoplasmic reticulum (ER) stress. Selenium, an inorganic micronutrient, has several cytoprotective properties, but its potential protective action against ZEL-induced apoptosis in trophoblast cells and the precise mechanisms remain unclear. In this study, we investigated the effects of sodium selenite, a predominant chemical form of selenium, on cell viability, apoptosis, and progesterone (P) production in ZEL-treated goat trophoblast cell line and explored the underlying molecular mechanisms. ZEL treatment repressed cell viability and promoted apoptosis, which was accompanied by an enhancement of the activity of caspase 3, a key executioner of apoptosis. ZEL treatment was involved in the upregulation of malonaldehyde (MDA) levels and was implicated in the reduction of the protein expression of selenoprotein S (SELS), thereby triggering protein expression of ER stress biomarkers (glucose-regulated protein 78 (GRP78) and CCAAT/enhancer-binding protein homologous protein (CHOP)). However, sodium selenite attenuates these adverse effects, including increases in apoptotic rate, caspase 3 activity, MDA, GRP78, and CHOP expression and decreases in SELS expression in cells treated with ZEL or Thapsigargin (Tg, an ER stress agonist). Simultaneously, 4-phenylbutyric acid (4-PBA, an ER stress antagonist) treatment significantly alleviated the ZEL-induced deleterious effects on cells in response to ZEL, similarly to sodium selenite. In addition, sodium selenite supplementation effectively rescued the ZEL-induced decrease in P production in ZEL-treated cells. In summary, these findings suggest that ZEL triggers apoptosis in goat trophoblast cells by downregulating SELS expression and activating the ER stress signaling pathway and that sodium selenite protects against these detrimental effects. This study provides novel insights into the benefits of using selenium against ZEL-induced apoptosis and cellular damage.
玉米赤霉烯酮（ZEL）诱导的不同细胞凋亡是通过各种分子机制介导的，包括内质网（ER）应激。硒是一种无机微量营养素，具有多种细胞保护特性，但它对滋养层细胞中 ZEL 诱导的细胞凋亡的潜在保护作用及其确切机制尚不清楚。在这项研究中，我们研究了亚硒酸钠（硒的主要化学形式）对 ZEL 处理的山羊滋养层细胞系中细胞活力、细胞凋亡和孕酮（P）产生的影响，并探讨了潜在的分子机制。ZEL 处理抑制细胞活力并促进细胞凋亡，同时伴随着半胱天冬酶 3（细胞凋亡的关键执行者）活性的增强。ZEL 处理涉及丙二醛（MDA）水平的上调，并涉及硒蛋白 S（SELS）蛋白表达的减少，从而触发 ER 应激生物标志物（葡萄糖调节蛋白 78（GRP78）和 CCAAT/增强子结合蛋白同源蛋白（CHOP））的蛋白表达。然而，亚硒酸钠减轻了这些不利影响，包括细胞凋亡率、半胱天冬酶 3 活性、MDA、GRP78 和 CHOP 表达的增加，以及 SELS 表达的减少，细胞用 ZEL 或 Thapsigargin（Tg，内质网应激激动剂）处理。同时，4-苯基丁酸（4-PBA，内质网应激拮抗剂）处理可显著缓解 ZEL 对细胞的有害影响，与亚硒酸钠类似。此外，亚硒酸钠补充剂有效挽救了 ZEL 处理细胞中 ZEL 诱导的 P 产生减少。总之，这些发现表明 ZEL 通过下调 SELS 表达和激活内质网应激信号通路在山羊滋养层细胞中引发细胞凋亡，亚硒酸钠可以防止这些有害影响。本研究为利用硒对抗 ZEL 诱导的细胞凋亡和细胞损伤提供了新的见解。
