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

Abstract

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.

• Authors: Bingwei Yang, Zhishuai Ye, Xiangyu Zhu, Rongchong Huang, Erqun Song, Yang Song
• Journal: Journal of hazardous materials (J Hazard Mater) Vol. 457 Pg. 131697 (09 05 2023) ISSN: 1873-3336 [Electronic] Netherlands
• PMID: 37257380 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2023 Elsevier B.V. All rights reserved.

Chemical References

• 2,3,5-trichloro-6-phenyl-(1,4)benzoquinone
• Polychlorinated Biphenyls
• Caveolin 1
• quinone
• Quinones

Topics

• Animals
• Mice
• Polychlorinated Biphenyls (toxicity)
• Phosphorylation
• Caveolin 1 (genetics)
• Quinones
• Atherosclerosis (chemically induced)