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经紫外光辐照降解的聚乙烯微塑料的处理导致溶酶体失调的细胞死亡。

Treatment of polyethylene microplastics degraded by ultraviolet light irradiation causes lysosome-deregulated cell death.

机构信息

School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka, 565-0871, Japan.

Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka, 565-0871, Japan.

出版信息

Sci Rep. 2024 Oct 14;14(1):24008. doi: 10.1038/s41598-024-74800-y.

Abstract

BACKGROUND

Microplastics (MPs), plastic particles < 5 mm in size, are prevalent in the environment, and human exposure to them is inevitable. To assess the potential risk of MPs on human health, it is essential to consider the physicochemical properties of environmental MPs, including polymer types, size, shape, and surface chemical modifications. Notably, environmental MPs undergo degradation due to external factors such as ultraviolet (UV) rays and waves, leading to changes in their surface characteristics. However, limited knowledge exists regarding the health effects of MPs, with a specific focus on their surface degradation. This study concentrates on cytotoxic MPs with surface degradation through UV irradiation, aiming to identify the mechanisms underlying their cell toxicity.

RESULTS

Polyethylene (PE) and surface-degraded PE achieved through UV light irradiation were employed as model MPs in this study. We explored the impact of PE and degraded PE on cell death in murine macrophage cell line RAW264.7 cells and human monocyte cell line THP-1 cells. Flow cytometric analysis revealed that degraded PE induced programmed cell death without activating caspase 3, while non-degraded PE did not trigger programmed cell death. These findings suggest that degraded PE might induce programmed cell death through mechanisms other than caspase-driven apoptosis. To understand the mechanisms of cell death, we investigated how cells responded to degraded PE-induced cellular stress. Immunofluorescence and western blotting analyses demonstrated that degraded PE induced autophagosome formation and increased p62 expression, indicating inhibited autophagy flux after exposure to degraded PE. Furthermore, degraded PE exposure led to a decrease in acidic lysosomes, indicating lysosomal dysregulation. These results imply that degraded PE induces lysosomal dysfunction, subsequently causing autophagy dysregulation and cell death.

CONCLUSIONS

This study unveils that UV-induced degradation of PE results in cell death attributed to lysosomal dysfunction. The findings presented herein provide novel insights into the effects of surface-degraded MPs on biological responses.

摘要

背景

微塑料(MPs)是粒径小于 5 毫米的塑料颗粒,广泛存在于环境中,人类不可避免地会接触到它们。为了评估 MPs 对人类健康的潜在风险,必须考虑环境 MPs 的物理化学特性,包括聚合物类型、尺寸、形状和表面化学修饰。值得注意的是,由于紫外线(UV)射线和波等外部因素,环境 MPs 会发生降解,导致其表面特性发生变化。然而,目前对于 MPs 的健康影响知之甚少,特别是对于其表面降解的影响。本研究集中于通过紫外线照射发生表面降解的细胞毒性 MPs,旨在确定其细胞毒性的机制。

结果

本研究采用聚乙烯(PE)和经紫外线光照表面降解的 PE 作为模型 MPs,探讨了 PE 和降解 PE 对 RAW264.7 鼠巨噬细胞系和 THP-1 人单核细胞系细胞死亡的影响。流式细胞术分析显示,降解 PE 诱导程序性细胞死亡而不激活 caspase 3,而非降解 PE 则不引发程序性细胞死亡。这些发现表明,降解 PE 可能通过 caspase 非依赖性凋亡以外的机制诱导程序性细胞死亡。为了了解细胞死亡的机制,我们研究了细胞对降解 PE 诱导的细胞应激的反应。免疫荧光和 Western blot 分析表明,降解 PE 诱导自噬体形成和 p62 表达增加,表明降解 PE 暴露后自噬流受到抑制。此外,降解 PE 暴露导致酸性溶酶体减少,表明溶酶体失调。这些结果表明,降解 PE 诱导溶酶体功能障碍,随后导致自噬失调和细胞死亡。

结论

本研究揭示了 PE 经紫外线诱导降解导致细胞死亡归因于溶酶体功能障碍。本研究结果为表面降解 MPs 对生物反应的影响提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d434/11473831/efb6606f21e2/41598_2024_74800_Fig1_HTML.jpg

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