Secretogranin III upregulation is involved in parkinsonian toxin-mediated astroglia activation.
Secretogranin III upregulation is involved in parkinsonian toxin-mediated astroglia activation.
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DOI：
10.2131/jts.45.271
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发表时间：
2020
期刊：
影响因子：
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通讯作者：
Xiaoni Zhan;Gehua Wen;Enzhu Jiang;Feng-rui Li;Xu Wu;H. Pang
中科院分区：
文献类型：
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作者：
Xiaoni Zhan;Gehua Wen;Enzhu Jiang;Feng-rui Li;Xu Wu;H. Pang
环境神经毒素如百草枯（PQ）、锰和1-1-甲基-4-苯基-1，2，3，6-四氢吡啶（MPTP）与帕金森病（PD）的高风险相关。这些帕金森病毒素对星形胶质细胞产生某些常见的毒理学作用，然而，它们在星形胶质细胞分泌蛋白的调节功能中的作用仍不清楚。在以前的研究中，我们观察到分泌颗粒蛋白II（SCG 2）和分泌颗粒蛋白III（SCG 3），这是调节分泌途径的重要组成部分，在PQ激活的U118星形胶质细胞升高。在当前的研究中，我们使用帕金森病毒素多巴胺（DA）、MPTP的活性代谢物（MPP+）、MnCl 2和脂多糖（LPS）作为诱导剂，研究了SCG 2和SCG 3的潜在调节作用。我们的研究结果表明，所有的帕金森毒素，除了LPS影响星形胶质细胞的活力，但不引起凋亡。暴露于DA，MPP+，和MnCl 2上调胶质细胞酸性蛋白（GFAP），星形胶质细胞活化的标志物，并刺激几个星形胶质细胞衍生因子的水平。此外，DA，MPP+，和氯化锰曝光阻碍星形胶质细胞周期的进展。此外，SCG 3的表达升高，而其外分泌抑制在帕金森毒素激活的星形胶质细胞。SCG 2水平保持不变。结合我们以前的研究结果，本研究的结果表明，SCG 3可能作为一个辅因子在星形胶质细胞激活刺激的各种毒素，和SCG 3的调节可能参与的毒理学机制，帕金森毒素影响星形胶质细胞。
Environmental neurotoxins such as paraquat (PQ), manganese, and 1-1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) are associated with a higher risk of Parkinson's disease (PD). These parkinsonian toxins exert certain common toxicological effects on astroglia; however, their role in the regulatory functions of astroglial secretory proteins remains unclear. In a previous study, we observed that secretogranin II (SCG2) and secretogranin III (SCG3), which are important components of the regulated secretory pathway, were elevated in PQ-activated U118 astroglia. In the current study, we used the parkinsonian toxins dopamine (DA), active metabolite of MPTP (MPP+), MnCl2, and lipopolysaccharide (LPS) as inducers, and studied the potential regulation of SCG2 and SCG3. Our results showed that all the parkinsonian toxins except LPS affected astroglial viability but did not cause apoptosis. Exposure to DA, MPP+, and MnCl2 upregulated glial fibrillary acidic protein (GFAP), a marker for astrocyte activation, and stimulated the levels of several astrocytic-derived factors. Further, DA, MPP+, and MnCl2 exposure impeded astroglial cell cycle progression. Moreover, the expression of SCG3 was elevated, while its exosecretion was inhibited in astroglia activated by parkinsonian toxins. The level of SCG2 remained unchanged. In combination with our previous findings, the results of this study indicate that SCG3 may act as a cofactor in astrocyte activation stimulated by various toxins, and the regulation of SCG3 could be involved in the toxicological mechanism by which parkinsonian toxins affect astroglia.