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3,3',4,4'-tetrachlorobiphenyl (PCB77) enhances human Kv1.3 channel currents and alters cytokine production

  • Jong-Hui Kim (Department of Physiology, Institute of Bioscience and Biotechnology, Kangwon National University School of Medicine ) ;
  • Soobeen Hwang (Department of Physiology, Institute of Bioscience and Biotechnology, Kangwon National University School of Medicine ) ;
  • Seo-In Park (Department of Physiology, Institute of Bioscience and Biotechnology, Kangwon National University School of Medicine ) ;
  • Hyo-Ji Lee (Department of Biological Sciences and Kangwon Radiation Convergence Research Support Center, Kangwon National University) ;
  • Yu-Jin Jung (Interdisciplinary Graduate Program in BIT Medical Convergence) ;
  • Su-Hyun Jo (Department of Physiology, Institute of Bioscience and Biotechnology, Kangwon National University School of Medicine )
  • 투고 : 2024.03.25
  • 심사 : 2024.04.18
  • 발행 : 2024.07.01

초록

Polychlorinated biphenyls (PCBs) were once used throughout various industries; however, because of their persistence in the environment, exposure remains a global threat to the environment and human health. The Kv1.3 and Kv1.5 channels have been implicated in the immunotoxicity and cardiotoxicity of PCBs, respectively. We determined whether 3,3',4,4'-tetrachlorobiphenyl (PCB77), a dioxin-like PCB, alters human Kv1.3 and Kv1.5 currents using the Xenopus oocyte expression system. Exposure to 10 nM PCB77 for 15 min enhanced the Kv1.3 current by approximately 30.6%, whereas PCB77 did not affect the Kv1.5 current at concentrations up to 10 nM. This increase in the Kv1.3 current was associated with slower activation and inactivation kinetics as well as right-shifting of the steady-state activation curve. Pretreatment with PCB77 significantly suppressed tumor necrosis factor-α and interleukin-10 production in lipopolysaccharide-stimulated Raw264.7 macrophages. Overall, these data suggest that acute exposure to trace concentrations of PCB77 impairs immune function, possibly by enhancing Kv1.3 currents.

키워드

과제정보

The authors wish to thank Prof. Han Choe (Department of Physiology, Bio-Medical Institute of Technology, University of Ulsan College of Medicine, Seoul, Korea) for providing the human Kv1.3 and Kv1.5 genes.

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