Neuroinflammation is a feature common to neurodegenerative diseases, such as Parkinson’s disease (PD), which might be responsive to therapeutic intervention. Rotenone has been widely used to establish PD models by inducing mitochondrial dysfunction and inflammation. Our previous studies have reported that pyrroloquinoline quinone (PQQ), a naturally occurring redox cofactor, could prevent mitochondrial dysfunction in rotenone induced PD models by regulating mitochondrial functions. In the present study, we aimed to investigate the effect of PQQ on neuroinflammation and the mechanism involved. BV2 microglia cells were pre-treated with PQQ followed by rotenone incubation. The data showed that PQQ did not affect the cell viability of BV2 cells treated with rotenone, while the conditioned medium (CM) of BV2 cells pre-treated with PQQ significantly increased cell viability of SH-SY5Y cells. In rotenone-treated BV2 cells, PQQ dose-dependently decreased lactate dehydrogenase (LDH) release and suppressed the up-regulation of pro-inflammation factors, such as interleukin-1β (IL-1β), IL-6 and tumor necrosis factor-α (TNF-α) in the cultured media, as well as nitric oxide (NO) release induced by rotenone. PQQ pretreatment also increased the ratio of LC3-II/LC3-I and expression of Atg5 in BV2 cells stimulated with rotenone. Additionally, the autophagosome observed by transmission electron microscopy (TEM) and co-localization of mitochondria with lysosomes indicated that mitophagy was induced by PQQ in rotenone-injured BV2 cells, and the PINK1/parkin mediated mitophagy pathway was regulated by PQQ. Further, autophagy inhibitor, 3-methyladenine (3-MA), partially abolished the neuroprotective effect of PQQ and attenuated the inhibition of inflammation with PQQ pretreatment. Taken together, our data extend our understanding of the neuroprotective effect of PQQ against rotenone-induced injury and provide evidence that autophagy enhancement might be a novel therapeutic strategy for PD treatment.

中文翻译：

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吡咯喹啉醌通过增强自噬抑制鱼藤酮诱导的小胶质细胞炎症

神经炎症是神经退行性疾病（例如帕金森病 (PD)）的常见特征，可能对治疗干预有反应。鱼藤酮通过诱导线粒体功能障碍和炎症被广泛用于建立 PD 模型。我们之前的研究报道，吡咯并喹啉醌 (PQQ) 是一种天然存在的氧化还原辅因子，可以通过调节线粒体功能来预防鱼藤酮诱导的 PD 模型中的线粒体功能障碍。在本研究中，我们旨在研究 PQQ 对神经炎症的影响及其机制。BV2 小胶质细胞用 PQQ 预处理，然后进行鱼藤酮孵育。数据显示PQQ不影响鱼藤酮处理的BV2细胞的细胞活力，而用 PQQ 预处理的 BV2 细胞的条件培养基 (CM) 显着提高了 SH-SY5Y 细胞的细胞活力。在鱼藤酮处理的 BV2 细胞中，PQQ 剂量依赖性地减少乳酸脱氢酶 (LDH) 的释放并抑制促炎因子的上调，如白细胞介素-1β (IL-1β)、IL-6 和肿瘤坏死因子-α (TNF-α) 以及鱼藤酮诱导的一氧化氮 (NO) 释放。PQQ 预处理还增加了鱼藤酮刺激的 BV2 细胞中 LC3-II/LC3-I 的比率和 Atg5 的表达。此外，透射电子显微镜 (TEM) 观察到的自噬体和线粒体与溶酶体的共定位表明 PQQ 在鱼藤酮损伤的 BV2 细胞中诱导了线粒体自噬，而 PINK1/parkin 介导的线粒体自噬途径受 PQQ 调节。更多，自噬抑制剂 3-甲基腺嘌呤 (3-MA) 部分消除了 PQQ 的神经保护作用，并减弱了 PQQ 预处理对炎症的抑制。总之，我们的数据扩展了我们对 PQQ 对鱼藤酮诱导的损伤的神经保护作用的理解，并提供了证据表明自噬增强可能是一种新的 PD 治疗策略。