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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Activation of pannexin-1 mediates triglyceride-induced macrophage cell death

  • Jung, Byung Chul (Department of Nutritional Sciences and Toxicology, University of California, Berkeley) ;
  • Kim, Sung Hoon (Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University) ;
  • Lim, Jaewon (Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University) ;
  • Kim, Yoon Suk (Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University)
  • Received : 2020.08.27
  • Accepted : 2020.09.28
  • Published : 2020.11.30
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Abstract

The accumulation of triglycerides (TGs) in macrophages induces cell death, a risk factor in the pathogenesis of atherosclerosis. We had previously reported that TG-induced macrophage death is triggered by caspase-1 and -2, therefore we investigated the mechanism underlying this phenomenon. We found that potassium efflux is increased in TG-treated THP-1 macrophages and that the inhibition of potassium efflux blocks TG-induced cell death as well as caspase-1 and -2 activation. Furthermore, reducing ATP concentration (known to induce potassium efflux), restored cell viability and caspase-1 and -2 activity. The activation of pannexin-1 (a channel that releases ATP), was increased after TG treatment in THP-1 macrophages. Inhibition of pannexin-1 activity using its inhibitor, probenecid, recovered cell viability and blocked the activation of caspase-1 and -2 in TG-treated macrophages. These results suggest that TG-induced THP-1 macrophage cell death is induced via pannexin-1 activation, which increases extracellular ATP, leading to an increase in potassium efflux.

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References

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