Jostes Haley C, Hickman Elise, Solosky Amie M, Chappel Jessie R, Vincent Emily C, Kim Yong Ho, Gilmour M Ian, Rager Julia E, Baker Erin S
Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States.
Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States.
Sci Total Environ. 2025 Oct 20;1000:180396. doi: 10.1016/j.scitotenv.2025.180396. Epub 2025 Sep 11.
Wildfire smoke is a growing concern due to continually rising exposures and links to numerous adverse health effects. Lipids are essential regulators of cellular health, yet their changes from wildfire smoke remain uncharacterized. To investigate molecular alterations driven by smoke inhalation, a lipidomic analysis of lung tissue from mice exposed to various wildfire simulations was performed. Smoke condensates were generated from three biomasses (pine needle, pine core, and eucalyptus) combusted under flaming (640 °C) and smoldering (500 °C) conditions. Six mouse groups were subjected to the different smoke condensate exposures, in addition to saline and lipopolysaccharide negative and positive control groups. Lung tissues were collected 4 h post-exposure and analyzed using a multidimensional platform coupling liquid chromatography, ion mobility spectrometry, and mass spectrometry. A total of 355 unique lipids were identified. Statistical comparisons between each wildfire condition and negative controls revealed 4-7 significantly altered lipids per condition (p < 0.05 and logFC| ≥ 1). Notably, all exposures resulted in an increased abundance of monosialodihexosylgangliosides (GM3s), the structurally simplest type of ganglioside. GM3 enrichment contributes to the formation of specialized microdomains including caveolae and lipid rafts, which can alter cell function regulation. Thus, to understand influenced molecular pathways, transcriptomic signatures from the same samples were evaluated. Here, differential expression was observed for genes involved in ganglioside metabolism, biosynthesis, and those regulated by gangliosides. These findings demonstrate concurrent changes across the transcriptome and lipidome in response to biomass smoke with many differentially expressed genes also implicated in inflammation and cancer, highlighting potential downstream effects of exposure.
由于暴露风险持续上升以及与众多不良健康影响存在关联，野火烟雾日益受到关注。脂质是细胞健康的重要调节因子，然而它们在野火烟雾中的变化仍未得到明确表征。为了研究吸入烟雾所驱动的分子改变，对暴露于各种野火模拟环境下的小鼠肺组织进行了脂质组学分析。烟雾浓缩物由三种生物质（松针、松果和桉树叶）在明火（640°C）和阴燃（500°C）条件下燃烧产生。除了生理盐水以及脂多糖阴性和阳性对照组外，六个小鼠组接受了不同的烟雾浓缩物暴露。暴露4小时后收集肺组织，并使用耦合液相色谱、离子淌度光谱和质谱的多维平台进行分析。总共鉴定出355种独特的脂质。每种野火条件与阴性对照组之间的统计比较显示，每种条件下有4 - 7种脂质发生了显著变化（p < 0.05且|logFC|≥1）。值得注意的是，所有暴露均导致单唾液酸二己糖神经节苷脂（GM3s）丰度增加，GM3s是结构最简单的神经节苷脂类型。GM3的富集有助于形成包括小窝和脂筏在内的特殊微结构域，这可能会改变细胞功能调节。因此，为了了解受影响的分子途径，对相同样本的转录组特征进行了评估。在此，观察到参与神经节苷脂代谢、生物合成以及受神经节苷脂调节的基因存在差异表达。这些发现表明，响应生物质烟雾时，转录组和脂质组会同时发生变化，许多差异表达基因也与炎症和癌症有关，凸显了暴露的潜在下游效应。
