Copper oxide nanoparticles disrupt lysosomal function and promote foam cell formation in RAW264.7 macrophages

IF 4.8 3区医学 Q1 PHARMACOLOGY & PHARMACY

Toxicology Pub Date : 2025-02-21 DOI:10.1016/j.tox.2025.154101

Yilin Luo , Kun Zhang , Lejiao Mao , Meiling Tan , Xiaomei Dong , Na Li , Yuexing Zhou , Chengzhi Chen , Zhen Zou , Jun Zhang

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引用次数: 0

Abstract

Macrophage-derived foam cells are crucial in the development of atherosclerosis, a multifaceted and progressive disorder characterized by lipid and fibrous accumulation in major arteries. Copper oxide nanoparticles (CuONPs) have found widespread applications but their potential role in atherosclerosis remains understudied. In this study, we investigated the impact of CuONPs on foam cell formation in RAW264.7 macrophages. Our results showed that CuONPs, at concentrations as low as 10 μg/ml, significantly exacerbated foam cell formation induced by oxidized low-density lipoprotein (ox-LDL). Exposure to CuONPs stimulated LDL release and elevated the expression of NLRP3 inflammasome components, including NLRP3, Caspase-1, and IL-1β. Transmission electron microscopy (TEM) revealed accumulation of CuONPs within macrophage lysosomes, leading to disrupted lysosomal function. CuONPs-treated cells exhibited autophagosome accumulation due to impaired lysosomal degradation, as confirmed by Western blot analysis showing abnormal expression of LAMP-1 and LAMP-2 proteins. Flow cytometry analysis further demonstrated decreased lysosomal acidity in CuONPs-exposed cells. Our findings reveal a novel mechanism whereby CuONPs activate the inflammasome, disrupt lysosomal function, and hinder cholesterol efflux, thereby exacerbating the formation of macrophage-derived foam cells. These results highlight the potential risks of CuONPs exposure and provide important insights into the role of environmental particulate matter in the development of atherosclerosis.

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来源期刊

Toxicology 医学-毒理学

CiteScore

7.80

自引率

4.40%

发文量

222

审稿时长

23 days

期刊介绍： Toxicology is an international, peer-reviewed journal that publishes only the highest quality original scientific research and critical reviews describing hypothesis-based investigations into mechanisms of toxicity associated with exposures to xenobiotic chemicals, particularly as it relates to human health. In this respect "mechanisms" is defined on both the macro (e.g. physiological, biological, kinetic, species, sex, etc.) and molecular (genomic, transcriptomic, metabolic, etc.) scale. Emphasis is placed on findings that identify novel hazards and that can be extrapolated to exposures and mechanisms that are relevant to estimating human risk. Toxicology also publishes brief communications, personal commentaries and opinion articles, as well as concise expert reviews on contemporary topics. All research and review articles published in Toxicology are subject to rigorous peer review. Authors are asked to contact the Editor-in-Chief prior to submitting review articles or commentaries for consideration for publication in Toxicology.