UK Health Security Agency, Radiation Effects Department, Radiation Protection Science Division, Harwell Science Campus, Didcot, Oxfordshire OX11 0RQ, UK.
Laboratoire PIMM, CNRS, Arts et Métiers Institute of Technology, Cnam, HESAM Universite, 75013 Paris, France.
NanoImpact. 2024 Apr;34:100508. doi: 10.1016/j.impact.2024.100508. Epub 2024 Apr 23.
The objective of this investigation was to evaluate the influence of micro- and nanoplastic particles composed of polyethylene terephthalate (PET), a significant contributor to plastic pollution, on human brain vascular pericytes. Specifically, we delved into their impact on mitochondrial functionality, oxidative stress, and the expression of genes associated with oxidative stress, ferroptosis and mitochondrial functions. Our findings demonstrate that the exposure of a monoculture of human brain vascular pericytes to PET particles in vitro at a concentration of 50 μg/ml for a duration of 3, 6 and 10 days did not elicit oxidative stress. Notably, we observed a reduction in various aspects of mitochondrial respiration, including maximal respiration, spare respiratory capacity, and ATP production in pericytes subjected to PET particles for 3 days, with a mitochondrial function recovery at 6 and 10 days. Furthermore, there were no statistically significant alterations in mitochondrial DNA copy number, or in the expression of genes linked to oxidative stress and ferroptosis, but an increase of the expression of the gene mitochondrial transcription factor A (TFAM) was noted at 3 days exposure. These outcomes suggest that, at a concentration of 50 μg/ml, PET particles do not induce oxidative stress in human brain vascular pericytes. Instead, at 3 days exposure, PET exposure impairs mitochondrial functions, but this is recovered at 6-day exposure. This seems to indicate a potential mitochondrial hormesis response (mitohormesis) is incited, involving the gene TFAM. Further investigations are warranted to explore the stages of mitohormesis and the potential consequences of plastics on the integrity of the blood-brain barrier and intercellular interactions. This research contributes to our comprehension of the potential repercussions of nanoplastic pollution on human health and underscores the imperative need for ongoing examinations into the exposure to plastic particles.
本研究旨在评估由聚对苯二甲酸乙二醇酯（PET）组成的微纳米塑料颗粒对人脑血管周细胞的影响。具体而言，我们深入研究了其对线粒体功能、氧化应激以及与氧化应激、铁死亡和线粒体功能相关基因表达的影响。研究结果表明，在体外将人脑血管周细胞与浓度为 50μg/ml 的 PET 颗粒孵育 3、6 和 10 天，不会引起氧化应激。值得注意的是，我们观察到 3 天暴露于 PET 颗粒的周细胞中线粒体呼吸的多个方面（包括最大呼吸、备用呼吸能力和 ATP 产生）受到抑制，而在 6 和 10 天则恢复了线粒体功能。此外，线粒体 DNA 拷贝数或与氧化应激和铁死亡相关基因的表达没有统计学上的显著变化，但在 3 天暴露时观察到线粒体转录因子 A（TFAM）基因的表达增加。这些结果表明，在 50μg/ml 的浓度下，PET 颗粒不会引起人脑血管周细胞发生氧化应激。相反，在 3 天暴露时，PET 暴露会损害线粒体功能，但在 6 天暴露时会恢复。这似乎表明，在 3 天暴露时，可能会引发一种潜在的线粒体适应反应（mitohormesis），涉及 TFAM 基因。需要进一步的研究来探索 mitohormesis 的阶段以及塑料对血脑屏障完整性和细胞间相互作用的潜在影响。本研究有助于我们理解纳米塑料污染对人类健康的潜在影响，并强调了持续研究塑料颗粒暴露的必要性。
