Atmospheric PM2.5 induce autophagy and autophagic flux blockage in HUVEC cells via ROS/TXNIP signaling: Important role of metal components.

Autophagy was involved in vascular endothelial injury caused by PM2.5, which aggravated the pathogenesis of cardiovascular diseases. However, major toxic components and underlying mechanism responsible for PM2.5-induced autophagy remain unclear. In this study, the effects of water-extracted PM2.5 (WE-PM2.5) on autophagy in human umbilical vein endothelial cells (HUVEC) were studied. Our results showed WE-PM2.5 promoted autophagosome initiation and formation, meanwhile, lysosomal function was impaired, which further caused autophagic flux blockage in HUVEC cells. Furthermore, removal of metals alleviated WE-PM2.5-induced autophagic flux blockage, while the artificial metal mixture reproduced the WE-PM2.5 response. Mechanistically, ROS regulated autophagy-related proteins evidenced by BECN1, LC3B and p62 expression reversed by NAC pretreatment in WE-PM2.5-exposed cells. WE-PM2.5 also increased TXNIP expression mediated by ROS; moreover, knockdown of TXNIP in WE-PM2.5-exposed cells decreased BECN1 and LC3B expression, but had little effects on the expression of p62, CTSB, and CTSD, indicating WE-PM2.5-induced TXNIP was involved in autophagosome initiation and formation rather than autophagic degradation. Collectively, WE-PM2.5-induced ROS not only promoted autophagosome initiation and formation, but also inhibited autophagic degradation. However, as the downstream molecule of ROS, TXNIP was only involved in autophagosome initiation and formation. Importantly, WE-PM2.5-bound metals were largely responsible for autophagic flux blockage in HUVEC cells.

Internalization and cytotoxicity of polystyrene microplastics in human umbilical vein endothelial cells.

Ubiquitous micro(nano)plastics (MNPs) are emerging environmental pollutants, which pose a potential threat to human health. When MNPs enter the blood circulatory system, vascular endothelium is one of the most important target organs that directly interact with the MNPs. However, little is known about the cytotoxicity of MNPs to vascular endothelial cells. In this study, we investigated the uptake and cytotoxic effects of polystyrene MNPs with a particle size of 1 µm (1-µm PS-MNPs) on human umbilical vein endothelial cells (HUVECs) in vitro. Our study found that interaction between HUVECs and 1-µm PS-MNPs was at a very low level. Even at the high exposure concentration of 25 µg/mL, the percentage of HUVECs combined with fluorescent 1-µm PS-MNPs was only 3.80% using flow cytometry analysis. Moreover, there were no significant differences in inflammation, autophagy, reactive oxygen species (ROS) level, lactate dehydrogenase (LDH) release, and adhesion molecule expression following exposure to 1-µm PS-MNPs (5, 10, and 25 µg/mL) for 48 h, except for a remarkable decrease in cell viability at the extremely high concentration of 100 µg/mL. Herein, 1-µm PS-MNPs showed a low level of acute toxicity to HUVECs in vitro, and we expect these results contribute to the further risk assessment of MNPs on human health.

Low Levels of Perfluorooctanoic Acid Exposure Activates Steroid Hormone Biosynthesis through Repressing Histone Methylation in Rats.

Perfluorooctanoic acid (PFOA) is a persistent organic pollutant, which has endocrine-disrupting properties and can interfere with the synthesis and secretion of testicular steroid hormones, but the underlying molecular mechanisms are still not fully understood. In this study, we investigated the effects of low doses of PFOA exposure on testicular steroidogenesis in rats and revealed the role of histone modifications. It was found that the serum levels of progesterone, testosterone, and estradiol were significantly increased after 0.015 and 0.15 mg/kg of PFOA exposure, and the expression of Star, a key rate-limiting gene, was up-regulated, while other steroidogenic genes Cyp11a1, Hsd3b, Cyp17a1, and Hsd17b were down-regulated. In addition, the levels of multiple histone modifications (H3K9me1/2/3 and H3K9/18/23ac) were all significantly reduced by PFOA in rat testis. Histone H3K9 methylation is associated with gene silencing, while histone acetylation leads to gene activation. ChIP analysis further showed that H3K9me1/3 was significantly decreased in the promoter region of Star, while H3K18ac levels were down-regulated in other gene promoters. Accordingly, we suggest that low-level PFOA enhances StAR expression through the repression of H3K9me1/3, which stimulates steroid hormone production in rat testis. These results are expected to shed new light on the molecular mechanisms by which low-dose PFOA disturbs male reproductive endocrine from an epigenetic aspect and may be useful for human health risk assessment regarding environmental PFOA exposure.