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http://dx.doi.org/10.5483/BMBRep.2020.53.11.179

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)
Publication Information
BMB Reports / v.53, no.11, 2020 , pp. 588-593 More about this Journal
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.
Keywords
Cell death; Pannexin-1; Potassium efflux; THP-1 macrophages; Triglyceride (TG);
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