PO.MCB09.05 · 分子与细胞生物学
慢性电子烟气溶胶暴露诱导小鼠代谢、翻译与免疫重编程：一项血清蛋白质组学分析
Chronic E-cigarette aerosol exposure induces metabolic, translational, and immune reprogramming in mice: A serum proteomics analysis
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摘要 Abstract
中文摘要
背景：电子烟气溶胶暴露已被认为与炎症和氧化应激相关；然而，其全身性代谢效应仍知之甚少。由于循环血清蛋白能够捕捉早期生理扰动，我们利用受控小鼠模型考察了慢性电子烟暴露如何改变代谢、翻译与免疫通路。
方法：我们使C57BL/6小鼠慢性暴露于电子烟气溶胶10周，并设过滤空气对照组。采集血清样本，通过非靶向LC-MS/MS蛋白质组学进行分析。使用GO、KEGG、Hallmark及MSigDB免疫特征集进行基因集富集分析（GSEA），以识别代谢、氧化还原生物学、翻译调控及免疫信号在通路层面的改变。
结果：我们的研究发现，慢性电子烟气溶胶暴露引发代谢重编程，表现为与氧化磷酸化、脂肪酸代谢、丙酮酸代谢、囊泡运输及活性氧（ROS）解毒相关通路的显著富集。我们观察到氧化还原适应性蛋白和糖酵解蛋白（PKM、IDH1/2、NQO1、GSTM1/2、GSS）水平升高，提示向NADPH驱动的抗氧化代谢和线粒体重塑的转变，与全身性代谢应激一致。这种代谢转变伴随着强烈的翻译重编程，包括核糖核蛋白复合物组装和mRNA加工通路的富集。翻译相关因子（如eIF4A2）表达升高，进一步支持应激反应性翻译程序的激活。免疫分析显示自然杀伤（NK）细胞相关通路的选择性富集，提示慢性电子烟暴露后NK细胞功能特征发生改变。这种先天免疫的靶向性转变与所观察到的代谢和翻译重塑一致，因为NK细胞活性高度依赖于糖酵解和应激适应性翻译程序。
结论：慢性电子烟暴露导致小鼠代谢、翻译与免疫过程发生相互关联的改变。由此产生的向抗氧化和糖酵解通路、应激反应性翻译及免疫信号改变的转变，提示代谢-免疫串扰是电子烟毒性的一种早期全身性机制，值得通过代谢、翻译和免疫谱分析进行靶向验证。
查看英文原文 English abstract
Background: E-cigarette aerosol exposure has been associated with inflammation and oxidative stress; however, its systemic metabolic effects remain poorly understood. Because circulating serum proteins capture early physiological perturbations, we examined how chronic e-cigarette exposure alters metabolic, translational, and immune pathways using a controlled mouse model.
Methods: We subjected C57BL/6 mice to chronic exposure to e-cigarette aerosols for 10 weeks, with filtered-air controls. Serum samples were collected and analyzed through untargeted LC-MS/MS proteomics. Gene Set Enrichment Analysis (GSEA) was performed using GO, KEGG, Hallmark, and MSigDB immune signatures to identify pathway-level alterations in metabolism, redox biology, translational control, and immune signaling.
Results: Our findings reveal that chronic exposure to e-cigarette aerosols triggers metabolic reprogramming, marked by significant enrichment of pathways related to oxidative phosphorylation, fatty acid metabolism, pyruvate metabolism, vesicle trafficking, and detoxification of reactive oxygen species (ROS). We observed increased levels of redox-adaptive and glycolytic proteins (PKM, IDH1/2, NQO1, GSTM1/2, GSS), indicating a shift toward NADPH-driven antioxidant metabolism and mitochondrial remodeling, consistent with systemic metabolic stress. This metabolic shift was accompanied by strong translational reprogramming, including enrichment of ribonucleoprotein complex assembly and mRNA processing pathways. Increased expression of translation-associated factors, such as eIF4A2, further supported activation of an stress-responsive translational program. Immune analyses revealed selective enrichment of natural killer (NK) cell-associated pathways, indicating altered NK cell functional signatures following chronic e-cigarette exposure. This targeted shift in innate immunity is consistent with the observed metabolic and translational remodeling, as NK cell activity relies heavily on glycolytic and stress-adaptive translational programs.
Conclusion: Chronic e-cigarette exposure leads to interconnected changes in metabolic, translational, and immune processes in mice. The resultant shifts towards antioxidant and glycolytic pathways, stress-responsive translation, and altered immune signaling suggest that metabolic-immune crosstalk serves as an early systemic mechanism of vaping toxicity, warranting targeted validation through metabolic, translational, and immune profiling.
利益披露 Disclosure
R. Begum, None..
G. Muthusamy, None..
P. Vaddi, None.