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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Triglyceride induces DNA damage leading to monocyte death by activating caspase-2 and caspase-8

  • Byung Chul Jung (Department of Nutritional Sciences and Toxicology, University of California) ;
  • Hyun-Kyung Kim (Department of Biomedical Laboratory Science, College of Software and Digital Healthcare Convergence, Yonsei University) ;
  • Sung Hoon Kim (Department of Biomedical Laboratory Science, College of Software and Digital Healthcare Convergence, Yonsei University) ;
  • Yoon Suk Kim (Department of Biomedical Laboratory Science, College of Software and Digital Healthcare Convergence, Yonsei University)
  • Received : 2022.11.30
  • Accepted : 2022.12.29
  • Published : 2023.03.31
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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 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.

Keywords

Acknowledgement

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (NRF-2021R1G1A1094159) and by the Korea Nazarene University Research Grants (2022).

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