Short- and long-term polystyrene nano- and microplastic exposure promotes oxidative stress and divergently affects skin cell architecture and Wnt/beta-catenin signaling

Abstract

Nano- and microplastic particles (NMP) are strong environmental contaminants affecting marine ecosystems and human health. The negligible use of biodegradable plastics and the lack of knowledge about plastic uptake, accumulation, and functional consequences led us to investigate the short- and long-term effects in freshly isolated skin cells from mice. Using fluorescent NMP of several sizes (200 nm to 6 µm), efficient cellular uptake was observed, causing, however, only minor acute toxicity as metabolic activity and apoptosis data suggested, albeit changes in intracellular reactive species and thiol levels were observed. The internalized NMP induced an altered expression of various targets of the nuclear factor-2-related transcription factor 2 pathway and were accompanied by changed antioxidant and oxidative stress signaling responses, as suggested by altered heme oxygenase 1 and glutathione peroxide 2 levels. A highly increased beta-catenin expression under acute but not chronic NMP exposure was concomitant with a strong translocation from membrane to the nucleus and subsequent transcription activation of Wnt signaling target genes after both single-dose and chronic long-term NMP exposure. Moreover, fibroblast-to-myofibroblast transdifferentiation accompanied by an increase of α smooth muscle actin and collagen expression was observed. Together with several NMP-induced changes in junctional and adherence protein expression, our study for the first time elucidates the acute and chronic effects of NMP of different sizes in primary skin cells' signaling and functional biology, contributing to a better understanding of nano- and microplastic to health risks in higher vertebrates.

Assessing the Impact of Polyethylene Nano/Microplastic Exposure on Human Vaginal Keratinocytes

“…Notably, MUC1 mRNA levels remained upregulated after 17 days of treatment, possibly indicating that cells adapted to the chronic particle exposure and produced a thicker glycocalyx to contrast the uptake of N/MPLs. More in general, the lower toxic effect of N/MPLs highlighted with continuous exposure suggests cellular adaptation to stress, as also demonstrated by Schmidt et al [17]. However, the expression of the previously mentioned epigenetic enzymes showed a fluctuating pattern throughout the experimental points, and persisted altered even after 21 days of exposure, implying that the cell adaptation to N/MPLs might be only apparent.…”

“…These objects may release N/MPL particles when using them, which, combined with the ubiquitous presence of N/MPLs in the environment, such as in water or food [12], might determine the enrichment of N/MPLs in the body, hence representing a potential health threat for humans. Among the different entry routes, humans are exposed to N/MPLs through the epidermis, which is the most external tissue of the body, but few works have addressed the consequences of N/MPL exposure on mammalian keratinocytes [9,17]. Moreover, most of the studies performed on epithelial cells tested only PS nano/microparticles with a particle size that was relatively large with respect to cell dimensions [43], whilst it is widely accepted that as particle size decreases, interaction with tissue and individual cells increases.…”

“…So, β-catenin localisation might be related to the dual behaviour of vaginal keratinocytes exposed to different amounts of PE particles. Interestingly, Schmidt et al [17] demonstrated that individual components of the actin cytoskeleton (e.g., stress fibres, filipodia, lamellipodia, focal adhesions) were strongly changed upon PS N/MPL treatment, which also influenced Wnt/β-catenin signalling. However, our findings suggested that whole β-catenin protein levels were diminished in PE N/MPL-treated cells at both concentrations compared to vehicle, as it was E-Cadherin expression, probably reflecting the disassembly of adherens junctions and loss of cell adhesion [54].…”

“…In order to facilitate studies on PE N/MPL biological effects, we selected two different particle concentrations (25 and 250 µg/mL) based on the findings of Gopinath et al [9] and Schmidt et al [17] on human and mouse skin keratinocytes. After 48 h of treatment, we noted a morphological change in VK2 E6/E7 cells, which showed peculiar vesicular formations (Figure 1a).…”

Biodegradation of Typical Plastics: From Microbial Diversity to Metabolic Mechanisms

“…The accumulation of microplastics has been found in many marine organisms, such as fish [ 12 , 13 ], oysters [ 14 ], and scallops [ 15 ], crossing various biological barriers to reach organs and disrupting cellular metabolic activity. Nanomicroplastics are usually more elusive, with higher threats leading to cellular oxidative stress and metabolic disorder [ 16 , 17 ]. These newly emerging pollutants are troublesome to marine ecological health.…”