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KMID : 0624620230560030166
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BMB Reports
2023 Volume.56 No. 3 p.166 ~ p.171
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Triglyceride induces DNA damage leading to monocyte death by activating caspase-2 and caspase-8
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Jung Byung-Chul
Kim Hyun-Kyung
Kim Sung-Hoon
Kim Yoon-Suk
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Abstract
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Monocytes are peripheral leukocytes that function in innate immunity. Excessive triglyceride (TG) accumulation causes monocyte death and thus can compromise innate immunity. However, the mechanisms by which TG mediates monocyte death remain unclear to date. Thus, this study aimed to elucidate the mechanisms by which TG induces monocyte death. Results showed that TG induced monocyte death by activating caspase-3/7 and promoting poly (ADP-ribose) polymerase (PARP) cleavage. In addition, TG induced DNA damage and activated the ataxia telangiectasia mutated (ATM)/checkpoint kinase 2 and ATM-and Rad3-related (ATR)/checkpoint kinase 1 pathways, leading to the cell death. Furthermore, TG-induced DNA damage and monocyte death were mediated by caspase-2 and -8, and caspase-8 acted as an upstream molecule of caspase-2. Taken together, these results suggest that TG-induced monocyte death is mediated via the caspase-8/caspase-2/DNA damage/executioner caspase/PARP pathways.
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KEYWORD
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Caspase-2, Caspase-8, DNA damage, Monocyte death, Triglycerides
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