Activation of pannexin-1 mediates triglyceride-induced macrophage cell death
Autor: | Jaewon Lim, Sung-Hoon Kim, Byung Chul Jung, Yoon Suk Kim |
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Rok vydání: | 2020 |
Předmět: |
Cell death
Programmed cell death Cell Survival THP-1 Cells Potassium chemistry.chemical_element Nerve Tissue Proteins Biochemistry Connexins Article Potassium efflux Pathogenesis Extracellular Humans Macrophage Triglyceride (TG) Viability assay THP-1 macrophages Molecular Biology Triglycerides Probenecid Macrophages Caspase 1 Caspase 2 Pannexin-1 General Medicine Pannexin Atherosclerosis Cell biology chemistry Efflux |
Zdroj: | BMB Reports |
ISSN: | 1976-670X |
Popis: | 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. [BMB Reports 2020; 53(11): 588-593]. |
Databáze: | OpenAIRE |
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