Increased clearance of non-biodegradable polystyrene nanoplastics by exocytosis through inhibition of retrograde intracellular transport

Abstract

Nanoplastics (NPs) are derived from microplastics and may cause health problems. We previously showed that 100 nm polystyrene (PS)-NPs enter cells, including mouse embryonic fibroblasts (MEFs), and their intracellular accumulation induces inflammatory and oxidative stress. Moreover, PS-NP uptake was found to occur via endocytosis, and they accumulated mostly at the juxtanuclear position, but never within the nucleus. We speculated that PS-NPs were cleared from cells when they were no longer exposed to PS-NPs. However, the effects of PS-NPs on the cellular machinery remain unknown. The accumulation of PS-NPs at the juxtanuclear position may be due to retrograde transport along microtubules. To confirm this, we treated PS-NP-exposed MEFs with inhibitors of histone deacetylase 6 (HDAC6), dynein, or microtubule polymerization and found greatly diminished intracellular and juxtanuclear accumulation. Moreover, rapid clearance of PS-NPs was observed when MEFs were treated with an HDAC6 inhibitor. PS-NPs were removed by exocytosis, as confirmed by treatment with an exocytosis inhibitor. Furthermore, inhibiting the retrograde transport of PS-NPs alleviated the activation of the antioxidant response pathway, inflammatory and oxidative stress, and reactive oxygen species generation. In summary, inhibition of the retrograde transport of non-biodegradable PS-NPs leads to their rapid export by exocytosis, which may reduce their cytotoxicity.