The adverse effects of air pollutants including particulate matter (PM) on the central nervous system is increasingly reported by epidemiological, animal and post-mortem studies in the last decade. Oxidative stress and inflammation are key consequences of exposure to PM although little is known of the exact mechanism. The association of PM exposure with deteriorating brain health is speculated to be driven by PM entry via the olfactory system. How air pollutants affect this key entry site remains elusive. In this study, we investigated effects of urban size-segregated PM on a novel cellular model: primary human olfactory mucosal (hOM) cells. Metabolic activity was reduced following 24-h exposure to PM without evident signs of toxicity. Results from cytometric bead array suggested a mild inflammatory response to PM exposure. We observed increased oxidative stress and caspase-3/7 activity as well as perturbed mitochondrial membrane potential in PM-exposed cells. Mitochondrial dysfunction was further verified by a decrease in mitochondria-dependent respiration. Transient suppression of the mitochondria-targeted gene, neuronal pentraxin 1 (NPTX1), was carried out, after being identified to be up-regulated in PM2.5–1 treated cells via RNA sequencing. Suppression of NPTX1 in cells exposed to PM did not restore mitochondrial defects resulting from PM exposure. In contrast, PM-induced adverse effects were magnified in the absence of NPTX1, indicating a critical role of this protein in protection against PM effects in hOM cells. Key mitochondrial functions were perturbed by urban PM exposure in a physiologically relevant cellular model via a mechanism involving NPTX1. In addition, inflammatory response and early signs of apoptosis accompanied mitochondrial dysfunction during exposure to PM. Findings from this study contribute to increased understanding of harmful PM effects on human health and may provide information to support mitigation strategies targeted at air pollution.

中文翻译：

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城市空气颗粒物会导致人类嗅粘膜细胞线粒体功能障碍。

过去十年中，流行病学、动物和尸检研究越来越多地报道了包括颗粒物 (PM) 在内的空气污染物对中枢神经系统的不利影响。氧化应激和炎症是接触 PM 的主要后果，尽管其确切机制知之甚少。据推测，PM 暴露与大脑健康恶化之间的关联是由 PM 通过嗅觉系统进入引起的。空气污染物如何影响这个关键的进入点仍然难以捉摸。在这项研究中，我们研究了城市规模隔离的 PM 对新型细胞模型：原代人类嗅粘膜 (hOM) 细胞的影响。暴露于 PM 24 小时后代谢活性降低，但没有明显的毒性迹象。细胞计数珠阵列的结果表明对 PM 暴露有轻微的炎症反应。我们观察到暴露于 PM 的细胞中氧化应激和 caspase-3/7 活性增加，以及线粒体膜电位受到干扰。线粒体依赖性呼吸的减少进一步证实了线粒体功能障碍。通过 RNA 测序确定线粒体靶向基因神经元五聚蛋白 1 (NPTX1) 在 PM2.5-1 处理的细胞中表达上调后，对线粒体靶向基因神经元五聚蛋白 1 (NPTX1) 进行了瞬时抑制。在暴露于 PM 的细胞中抑制 NPTX1 并不能恢复 PM 暴露引起的线粒体缺陷。相比之下，在缺乏 NPTX1 的情况下，PM 诱导的不利影响会被放大，表明该蛋白在保护 hOM 细胞免受 PM 影响方面发挥着关键作用。在生理相关的细胞模型中，通过涉及 NPTX1 的机制，关键线粒体功能受到城市 PM 暴露的干扰。此外，暴露于 PM 期间，炎症反应和细胞凋亡的早期迹象伴随着线粒体功能障碍。这项研究的结果有助于加深人们对 PM 对人类健康有害影响的了解，并可能提供信息来支持针对空气污染的缓解策略。