机构地区:[1]School of Environment,Hangzhou Institute for Advanced Study,University of Chinese Academy of Sciences,Hangzhou 310024,China [2]State Key Laboratory of Environmental Chemistry and Ecotoxicology,Research Center for Eco-Environmental Sciences,Chinese Academy of Sciences,Beijing 100085,China [3]Key Laboratory of Pollution Exposure and Health Intervention of Zhejiang Province,College of Biology and Environmental Engineering,Zhejiang Shuren University,Hangzhou 310015,China [4]University of Chinese Academy of Science,Beijing 100049,China [5]Hubei Key Laboratory of Environmental and Health Effects of Persistent Toxic Substances,School of Environment and Health,Jianghan University,Wuhan 430056,China [6]Key Laboratory of Protein and Peptide Pharmaceuticals&Laboratory of Proteomics,Institute of Biophysics,Chinese Academy of Sciences,Beijing 100101,China
出 处:《Journal of Environmental Sciences》2025年第4期395-411,共17页环境科学学报(英文版)
基 金:supported by the Key Research and Development Plan of Zhejiang Province(No.2021C03176);Zhejiang Provincial Natural Science Foundation of China(No.LY23B070001);the Key Laboratory of Pollution Exposure and Health Intervention of Zhejiang Province(No.20230009);the National Natural Science Foundation of China(No.22106032);the Strategic Priority Research Program of the Chinese Academy of Sciences(No.XDB0750000).
摘 要:Per-and polyfluoroalkyl substances(PFASs)can induce a range of adverse health effects,with the precise molecularmechanisms remaining elusive.Extracellular vesicles(EVs)have demonstrated their potential to elucidate unknown molecular mechanisms.Building upon the close alignment of their biological functions with the observed health effects of PFASs,this study innovatively focuses on proteomic insights from EVs into the molecular mechanisms underlying the systemic health effects of PFASs.Through rat exposure experiments and proteomics technology,it not only demonstrated the occurrence of PFASs in EVs but also revealed the alterations in the serum EVs and the expression of their protein cargos following mixed exposure to PFASs,leading to changes in related pathways.These changes encompass various biological processes,including proteasome activity,immune response,cytoskeletal organization,oxidative stress,cell signaling,and nervous system function.Particularly noteworthy is the uncovering of the activation of the proteasome pathway,highlighting significant key contributing proteins.These novel findings provide a new perspective for exploring the molecularmechanism underlying the systemic health effects of PFASs and offer reliable screening for potential biomarkers.Additionally,comparisons with serum confirmed the potential of serum EVs as biological responders and measurable endpoints for evaluating PFASs-induced toxicity.
关 键 词:Per-and polyfluoroalkyl substances Extracellular vesicles Health effects PROTEOMICS PROTEASOME
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