Rotenone directly induces BV2 cell activation via the p38 MAPK pathway.
Rotenone directly induces BV2 cell activation via the p38 MAPK pathway.
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Rotenone 通过 p38 MAPK 途径直接诱导 BV2 细胞激活。
DOI：
10.1371/journal.pone.0072046
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Wang G
中科院分区：
文献类型：
--
作者：
Gao F;Chen D;Hu Q;Wang G
帕金森病（Parkinson's disease，PD）是第二常见的神经退行性疾病。虽然其发病机制尚不清楚，但越来越多的证据表明，由环境毒素如线粒体复合物I抑制剂诱导的线粒体功能障碍在疾病过程中起着重要作用。PD脑内小胶质细胞高度活化，炎症也是PD发病机制中的重要因素。然而，这些毒素激活小胶质细胞的方式仍不清楚。在本研究中，我们发现鱼藤酮，线粒体复合物I抑制剂，可以直接激活小胶质细胞通过核因子-κ B（NF-κB）信号通路，从而诱导炎症细胞因子的表达显着增加。我们进一步观察到鱼藤酮诱导caspase-1激活和成熟IL-1β释放，这两者都严格依赖于p38丝裂原活化蛋白激酶（MAPK）。p38的激活与鱼藤酮产生的活性氧（ROS）的存在有关。这些ROS的去除废除了小胶质细胞的激活。因此，我们的数据表明，环境毒素鱼藤酮可以通过p38 MAPK通路直接激活小胶质细胞。
Parkinson’s disease (PD) is the second most common neurodegenerative disease. Although its pathogenesis is still unclear, increasing evidence suggests that mitochondrial dysfunction induced by environmental toxins, such as mitochondrial complex I inhibitors, plays a significant role in the disease process. The microglia in PD brains are highly activated, and inflammation is also an essential element in PD pathogenesis. However, the means by which these toxins activate microglia is still unclear. In the present study, we found that rotenone, a mitochondrial complex I inhibitor, could directly activate microglia via the nuclear factor kappa B (NF-κB) signaling pathway, thereby inducing significantly increased expression of inflammatory cytokines. We further observed that rotenone induced caspase-1 activation and mature IL-1β release, both of which are strictly dependent on p38 mitogen-activated protein kinase (MAPK). The activation of p38 is associated with the presence of reactive oxygen species (ROS) produced by rotenone. Removal of these ROS abrogated the activation of the microglia. Therefore, our data suggest that the environmental toxin rotenone can directly activate microglia through the p38 MAPK pathway.
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