T-2 Toxin Induces Apoptotic Cell Death and Protective Autophagy in Mouse Microglia BV2 Cells.
T-2 Toxin Induces Apoptotic Cell Death and Protective Autophagy in Mouse Microglia BV2 Cells.
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T-2毒素诱导小鼠小胶质细胞BV 2细胞凋亡和保护性自噬
DOI：
10.3390/jof8080761
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发表时间：
2022-07-22
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影响因子：
--
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中科院分区：
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T-2毒素暴露可引起神经毒性;然而，确切的分子机制仍不清楚。在本研究中，我们使用小鼠小胶质细胞BV 2细胞系研究T-2毒素诱导的细胞毒性和潜在的分子机制。结果表明，T-2毒素处理诱导的BV 2细胞的细胞毒性是剂量和时间依赖性的。与对照组相比，1.25-5 ng/mL的T-2毒素处理显著增加了活性氧（ROS）的产生并引发氧化应激。T-2毒素处理也引起BV 2细胞线粒体功能障碍，表现为线粒体跨膜电位降低，Bax蛋白表达上调，Bcl-2蛋白表达降低。同时，T-2毒素处理可上调Caspase-3和PARP-1蛋白的表达，下调HO-1和核Nrf 2蛋白的表达，诱导BV 2细胞凋亡。N-乙酰半胱氨酸（NAC）的补充显着减弱T-2毒素诱导的细胞毒性。此外，T-2毒素处理激活自噬并上调自噬流量，自噬的抑制显著促进T-2毒素诱导的细胞凋亡。综上所述，我们的研究结果表明，T-2毒素诱导的细胞毒性在BV 2细胞中涉及ROS的产生，线粒体凋亡途径的激活，和Nrf 2/HO-1途径的抑制。我们的研究为T-2毒素介导的神经毒性的潜在分子机制提供了新的见解。
T-2 toxin exposure could cause neurotoxicity; however, the precise molecular mechanisms remain unclear. In the present study, we investigated T-2 toxin-induced cytotoxicity and underlying molecular mechanisms using a mouse microglia BV2 cell line. The results show that T-2 toxin treatment-induced cytotoxicity of BV2 cells was dose- and time-dependent. Compared to the control, T-2 toxin treatment at 1.25–5 ng/mL significantly increased reactive oxygen species (ROS) production and triggered oxidative stress. T-2 toxin treatment also caused mitochondrial dysfunction in BV2 cells, which was evidenced by decreased mitochondrial transmembrane potential, upregulated expression of Bax protein, and decreased expression of Bcl-2 protein. Meanwhile, T-2 toxin treatment upregulated the expression of cleaved-caspase-3, cleaved-PARP-1 proteins, and downregulated the expression of HO-1 and nuclear Nrf2 proteins, finally inducing cell apoptosis in BV2 cells. N-acetylcysteine (NAC) supplementation significantly attenuated T-2 toxin-induced cytotoxicity. Moreover, T-2 toxin treatment activated autophagy and upregulated autophagy flux, and the inhibition of autophagy significantly promoted T-2 toxin-induced cell apoptosis. Taken together, our results reveal that T-2 toxin-induced cytotoxicity in BV2 cells involves the production of ROS, the activation of the mitochondrial apoptotic pathway, and the inhibition of the Nrf2/HO-1 pathway. Our study offers new insight into the underlying molecular mechanisms in T-2 toxin-mediated neurotoxicity.
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