Triglyceride induces DNA damage leading to monocyte death by activating caspase-2 and caspase-8

Byung Chul Jung; Hyun-Kyung Kim; Sung Hoon Kim; Yoon Suk Kim

doi:10.5483/BMBRep.2022-0201

Triglyceride induces DNA damage leading to monocyte death by activating caspase-2 and caspase-8

BMB Rep. 2023 Mar;56(2):166-171. doi: 10.5483/BMBRep.2022-0201.

Authors

Byung Chul Jung¹, Hyun-Kyung Kim², Sung Hoon Kim³, Yoon Suk Kim⁴

Affiliations

¹ Department of Nutritional Sciences and Toxicology, University of California, Berkeley, CA 94720, USA; Department of Biomedical Laboratory Science, College of Software and Digital Healthcare Convergence, Yonsei University, Wonju 26493, Korea.
² Department of Biomedical Laboratory Science, College of Software and Digital Healthcare Convergence, Yonsei University, Wonju 26493; Department of Biomedical Laboratory Science, College of Natural Science, Gimcheon University, Gimcheon 39528, Korea.
³ Department of Biomedical Laboratory Science, College of Software and Digital Healthcare Convergence, Yonsei University, Wonju 26493; Department of Biomedical Laboratory Science, Korea Nazarene University, Cheonan 31172, Korea.
⁴ Department of Biomedical Laboratory Science, College of Software and Digital Healthcare Convergence, Yonsei University, Wonju 26493, Korea.

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. [BMB Reports 2023; 56(3): 166-171].

Publication types

News

MeSH terms

Ataxia Telangiectasia Mutated Proteins / genetics
Caspase 2* / genetics
Caspase 2* / metabolism
Caspase 3 / metabolism
Caspase 8* / genetics
Caspase 8* / metabolism
Cell Cycle Proteins / metabolism
DNA Damage
Immunity, Innate* / immunology
Monocytes* / metabolism
Poly(ADP-ribose) Polymerase Inhibitors / pharmacology
Poly(ADP-ribose) Polymerases / metabolism
Triglycerides* / genetics
Triglycerides* / immunology

Substances

Ataxia Telangiectasia Mutated Proteins
Caspase 2
Caspase 3
Caspase 8
Cell Cycle Proteins
Poly(ADP-ribose) Polymerase Inhibitors
Poly(ADP-ribose) Polymerases
Triglycerides

Grants and funding

ACKNOWLEDGEMENTS 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).