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

J Hazard Mater. 2023 Sep 5;457:131697. doi: 10.1016/j.jhazmat.2023.131697. Epub 2023 May 24.


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.

Keywords: Atherosclerosis; Caveolin-1; Inflammation; PCBs; Quinone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Atherosclerosis* / chemically induced
  • Caveolin 1 / genetics
  • Mice
  • Phosphorylation
  • Polychlorinated Biphenyls* / toxicity
  • Quinones


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