Polychlorinated Biphenyl Quinone Promotes Atherosclerosis through Lipid Accumulation and Endoplasmic Reticulum Stress via CD36
| Autor: | Erqun Song, Bingwei Yang, Xuying Lv, Qi Qin, Yang Song, Lei Xu, Zixuan Liu |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
CD36 Antigens
Male medicine.medical_specialty Mice Knockout ApoE CD36 Metabolite Apoptosis 010501 environmental sciences Diet High-Fat Toxicology 01 natural sciences Mice Necrosis 03 medical and health sciences chemistry.chemical_compound Internal medicine Benzoquinones medicine Animals Protein kinase A 030304 developmental biology 0105 earth and related environmental sciences 0303 health sciences biology ATF6 Chemistry Kinase Endoplasmic reticulum General Medicine Atherosclerosis Endoplasmic Reticulum Stress Lipid Metabolism Polychlorinated Biphenyls Cholesterol RAW 264.7 Cells Endocrinology Cholesteryl ester biology.protein Cytokines Environmental Pollutants Tumor necrosis factor alpha |
| Zdroj: | Chemical Research in Toxicology. 33:1497-1507 |
| ISSN: | 1520-5010 0893-228X |
| Popis: | Polychlorinated biphenyls (PCBs) are persistent organic environmental pollutants. According to previous epidemiological reports, PCBs exposure is highly related to atherosclerosis. However, studies of PCBs metabolites and atherosclerosis and corresponding mechanism studies are scarce. In this study, we evaluated the effect of 2,3,5-trichloro-6-phenyl-[1,4]-benzoquinone (PCB29-pQ), a presumptive PCB metabolite, on atherosclerosis. Aortic plaques were increased in PCB29-pQ-treated ApoE-/- mice [intraperitoneally (i.p.) injection of 5 mg/kg body weight of PCB29-pQ once a week for 12 continuous weeks, high-fat feeding]. We observed lipids accumulation and the release of interleukin-1 beta (IL-1β), tumor necrosis factor alpha (TNF-α), and interleukin-6 (IL-6) in ApoE-/- mice. In addition, we found that PCB29-pQ promoted the levels of total cholesterol, free cholesterol, triglyceride, and cholesteryl ester. Mechanism investigation indicated that PCB29-pQ induces the activation of three branches of endoplasmic reticulum (ER) stress response, that is, phosphorylated protein kinase R-like ER kinase (p-PERK), eukaryotic translation initiation factor 2α (eIF2α) and transcription factor 6 (ATF6), which is responsible for downstream necrosis. More importantly, we found the silence of CD36 is able to reverse PCB29-pQ-induced adverse effects completely. Overall, PCB29-pQ exposure resulted in lipid accumulation, ER stress response, apoptosis, and pro-inflammatory cytokines release via CD36, ultimately leading to atherosclerosis. |
| Databáze: | OpenAIRE |
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