The redox activity of polychlorinated biphenyl quinone metabolite orchestrates its pro-atherosclerosis effect via CAV1 phosphorylation

• Published in: Journal of hazardous materials Vol. 457; p. 131697
• Main Authors: Yang, Bingwei, Ye, Zhishuai, Zhu, Xiangyu, Huang, Rongchong, Song, Erqun, Song, Yang
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 05.09.2023
• Subjects: Animals; Atherosclerosis; Atherosclerosis - chemically induced; Caveolin 1 - genetics; Caveolin-1; Inflammation; Mice; PCBs; Phosphorylation; Polychlorinated Biphenyls - toxicity; Quinone; Quinones; Caveolin-1; PCBs; Inflammation; Quinone; Atherosclerosis
• ISSN: 0304-3894; 1873-3336
• DOI: 10.1016/j.jhazmat.2023.131697

Further investigations are required to prove that polychlorinated biphenyls (PCBs) exposure is a cardiovascular disease risk factor. Unlike previous studies that attributed the atherogenic effect of PCBs to aryl hydrocarbon receptor activation, we illustrated a new mechanism involved in the redox reactivity of PCBs. We discover the redox reactivity of quinone moiety is the primary factor for PCB29-pQ-induced proinflammatory response, which highly depends on the status of caveolin 1 (CAV1) phosphorylation. PCB29-pQ-mediated CAV1 phosphorylation disrupts endothelial nitric oxide synthase, toll-like receptor 4, and reduces interleukin-1 receptor-associated kinase 1 binding with CAV1. Phosphorylated proteomics analysis indicated that PCB29-pQ treatment significantly enriched phosphorylated peptides in protein binding functions, inflammation, and apoptosis signaling. Meanwhile, apolipoprotein E knockout (ApoE-/-) mice exposed to PCB29-pQ had increased atherosclerotic plaques compared to the vehicle group, while this effect was significantly reduced in ApoE-/-/CAV1-/- double knockout mice. Thus, we hypothesis CAV1 is a platform for proinflammatory cascades induced by PCB29-pQ on atherosclerotic processes. Together, these findings confirm that the redox activity of PCB metabolite plays a role in the etiology of atherosclerosis. [Display omitted] •Quinone moiety is responsible for PCB29-pQ-induced proinflammatory response.•PCB29-pQ regulates the status of caveolin 1 (CAV1) phosphorylation.•PCB29-pQ-exposed mice had increased atherosclerotic plaques.•CAV knockout significant abrogated PCB29-pQ-induced proinflammatory cascades.