| Triglyceride induces DNA damage leading to monocyte death by activating caspase-2 and caspase-8 |
Byung Chul Jung  1,2,# (Research worker), Hyun-Kyung Kim 2,3,# ( Professor), Sung Hoon Kim 2,4 ( Professor), YoonSuk Kim 2,* ( Professor) |
1Department of Nutritional Sciences and Toxicology, University of California, Berkeley, State of California 94720, United States,
2Department of Biomedical Laboratory Science, College of Software and Digital Healthcare Convergence, Yonsei University, Wonju, Gangwon-do 26493, Republic of Korea,
3Department of Biomedical Laboratory Science, College of Natural Science, Gimcheon University, Gimcheon, Gyeongsangbuk-do 39528, Republic of Korea,
4Department of Biomedical Laboratory Science, Korea Nazarene University, Cheonan, Chungcheongnam-do 31172, Republic of Korea |
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Abstract
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 PARP cleavage. In addition, TG induced DNA damage and activated the ATM/Chk2 and ATR/Chk1 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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| Abstract, Accepted Manuscript(in press) [Submitted on November 30, 2022, Accepted on December 29, 2022] |
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