Benzotriazole ultraviolet stabilizer UV-234 promotes foam cell formation in RAW264.7 macrophages. (1st January 2023)

• Record Type: Journal Article
• Authors: Shen, Xinming; Hu, Wenxin; Xu, Chenke; Xu, Cheng; Wan, Yi; Hu, Jianying
• Is Part Of: Environmental pollution. Volume 316(2023)part 1
• Publication Date: 2023-01-01
• Subjects: UV-234 -- HIF1α -- Ubiquitin–proteasome system -- Liver X receptor; Pollution -- Periodicals; Pollution -- Environmental aspects -- Periodicals; Environmental Pollution -- Periodicals; Pollution -- Périodiques; Pollution -- Aspect de l'environnement -- Périodiques; Pollution -- Effets physiologiques -- Périodiques; Pollution; Pollution -- Environmental aspects; Periodicals; Electronic journals; 363.73
• DOI: 10.1016/j.envpol.2022.120560
• Languages: English
• ISSNs: 0269-7491

Abstract

Abstract: Benzotriazole ultraviolet stabilizers (BUVSs) have been reported to induce inflammatory responses which may promote cholesterol accumulation and to downregulate the expression of genes involved in cholesterol biosynthesis; hence, we speculated whether BUVSs promote foam cell formation, which plays a key role in all stages of atherosclerosis. Herein, we used high-content imaging to screen all available BUVSs; of all the 17 candidates, 6 of them could promote foam cell formation at 10 μM. Further analyses showed that one BUVS UV-234 markedly increased the foam cell staining intensity by 15.0%–55.9% in the 0.5–10 μM exposure groups in a dose-dependent manner. Cholesterol influx was markedly enhanced by 21.0%–24.5% in the 5–10 μM exposure groups and cholesterol efflux was downregulated by 21.2%–59.3% in the 0.5–10 μM exposure groups, indicating that cholesterol efflux may play a major role in foam formation considering cholesterol efflux was downregulated at a relatively low concentration. Gene expression of ABCA1 and ABCG1 which regulate the cholesterol efflux were also decreased at 0.5–10 μM. The degradation of hypoxia-inducible factor 1α (HIF1α) via the ubiquitin–proteasome system was observed at 0.5–10 μM, probably contributing to the downregulated expression of the genes encoding liver X receptors (LXR) α/β and their targets, ABCA1 and ABCG1 . Thus, our study revealed that BUVSs frequently detected in the environment can promote foam cell formation in macrophages, contributing to the risk of atherosclerosis in humans. Graphical abstract: Image 1 Highlights: 6 of 17 available benzotriazole ultraviolet stabilizers can promote foam cell formation. UV-234, widely detected in both the environment and the human, elicits the highest cholesterol accumulation. Foam cell formation, induced by UV-234, is mainly due to the downregulation of liver X receptors.