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

Yan-Yang Lu, Meiyi Cao, Fuping Li, Meiping Tian, Hongyun Ren, Qiaoqiao Chi, Qingyu Huang

Journal of hazardous materials 2023 Mar 05

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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. Copyright © 2022 Elsevier B.V. All rights reserved.

Citation

Yan-Yang Lu, Meiyi Cao, Fuping Li, Meiping Tian, Hongyun Ren, Qiaoqiao Chi, Qingyu Huang. Atmospheric PM2.5 induce autophagy and autophagic flux blockage in HUVEC cells via ROS/TXNIP signaling: Important role of metal components. Journal of hazardous materials. 2023 Mar 05;445:130623