Necrotic-like BV-2 microglial cell death due to methylmercury exposure.
Necrotic-like BV-2 microglial cell death due to methylmercury exposure.
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坏死样BV-2小胶质细胞死亡，导致甲基汞暴露。
DOI：
10.3389/fphar.2022.1003663
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发表时间：
2022
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
--
作者：
甲基汞（MeHg）是一种危险的环境污染物，在食物链中具有很强的生物蓄积性和神经毒性。在神经系统中，甲基汞可能导致神经发育受损，并可能干扰免疫反应，损害对神经炎症的适当控制，并加剧神经退化。人类暴露于甲基汞的环境污染，特别是在采矿或工业活动频繁的地区，这引起了公众健康问题。考虑到这一点，这项工作的目的是澄清途径，导致急性毒性效应所造成的甲基汞暴露在小胶质细胞。将BV-2小鼠小胶质细胞与不同浓度（0.01、0.1、1和10 µM）的甲基汞孵育1 h，然后连续暴露于脂多糖（LPS，0.5 μg/ml）6或24 h。细胞暴露后，活性氧（ROS），IL-6和TNF-α细胞因子的产生，诱导型一氧化氮合酶（iNOS）的表达，一氧化氮（NO）的释放，代谢活性，碘化丙啶（PI）的摄取，caspase-3和-9活性和吞噬活性进行了评估。10 μM甲基汞可降低BV-2细胞ROS的生成，减少促炎细胞因子IL-6、TNF-α、iNOS的产生和分泌，减少NO的释放。此外，与相应的对照组相比，10 µM甲基汞降低了BV-2的代谢活性，并增加了PI阳性细胞（坏死样细胞死亡）的数量。此外，甲基汞没有干扰caspase活性或细胞的吞噬功能。高浓度甲基汞对BV-2小胶质细胞的短期影响导致几种促炎介质的产生受损，以及小胶质细胞因坏死而死亡的增加，从而损害其神经炎症反应。阐明甲基汞引起的脑细胞神经毒性和神经变性的机制有助于更好地了解甲基汞暴露后的急性和长期慢性神经炎症反应。
Methylmercury (MeHg) is a dangerous environmental contaminant with strong bioaccumulation in the food chain and neurotoxic properties. In the nervous system, MeHg may cause neurodevelopment impairment and potentially interfere with immune response, compromising proper control of neuroinflammation and aggravating neurodegeneration. Human populations are exposed to environmental contamination with MeHg, especially in areas with strong mining or industrial activity, raising public health concerns. Taking this into consideration, this work aims to clarify pathways leading to acute toxic effects caused by MeHg exposure in microglial cells. BV-2 mouse microglial cells were incubated with MeHg at different concentrations (0.01, 0.1, 1 and 10 µM) for 1 h prior to continuous Lipopolysaccharide (LPS, 0.5 μg/ml) exposure for 6 or 24 h. After cell exposure, reactive oxygen species (ROS), IL-6 and TNF-α cytokines production, inducible nitric oxide synthase (iNOS) expression, nitric oxide (NO) release, metabolic activity, propidium iodide (PI) uptake, caspase-3 and -9 activities and phagocytic activity were assessed. MeHg 10 µM decreased ROS formation, the production and secretion of pro-inflammatory cytokines IL-6, TNF-α, iNOS immunoreactivity, the release of NO in BV-2 cells. Furthermore, MeHg 10 µM decreased the metabolic activity of BV-2 and increased the number of PI-positive cells (necrotic-like cell death) when compared to the respective control group. Besides, MeHg did not interfere with caspase activity or the phagocytic profile of cells. The short-term effects of a high concentration of MeHg on BV-2 microglial cells lead to impaired production of several pro-inflammatory mediators, as well as a higher microglial cell death via necrosis, compromising their neuroinflammatory response. Clarifying the mechanisms underlying MeHg-induced neurotoxicity and neurodegeneration in brain cells is relevant to better understand acute and long-term chronic neuroinflammatory responses following MeHg exposure.
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影响因子：
6.2
作者：
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通讯作者：
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