Biomedical Science Letters (대한의생명과학회지)

The Korean Society for Biomedical Laboratory Sciences (대한의생명과학회)
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Inducible Nitric Oxide Synthase Mediates the Triglyceride-induced Death of THP-1 Monocytes

  • 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) ;
  • Jaewon Lim (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 : 2023.05.10
  • Accepted : 2023.06.27
  • Published : 2023.06.30
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Abstract

Triglyceride (TG) accumulation can cause monocytic death and suppress innate immunity. However, the signaling pathways involved in this phenomenon are not fully understood. This study aimed to examine whether inducible nitric oxide synthase (iNOS) is involved in the TG-induced death of THP-1 monocytes. Results showed that iNOS was upregulated in TG-treated THP-1 monocytes, and iNOS inhibition blocked TG-induced monocytic death. In addition, TG-induced poly (ADP-ribose) polymerase (PARP) cleavage and caspase-3 and -7 activation were suppressed by iNOS inhibition. Furthermore, the expression of X-linked inhibitor of apoptosis protein (XIAP) and survivin, which inhibit caspase-3 and -7, was reduced in TG-treated THP-1 monocytes, but iNOS inhibition recovered the TG-induced downregulation of XIAP and survivin expression. Considering that TG-induced monocytic death is triggered by caspase2 and -8, we investigated whether caspase-2 and -8 are linked to the TG-induced expression of iNOS in THP-1 monocytes. When the activities of caspase-2 and -8 were inhibited by specific inhibitors, the TG-induced upregulation of iNOS and downregulation of XIAP and survivin were restored in THP-1 monocytes. These results suggest that TG-induced monocytic death is mediated by the caspase-2/caspase-8/iNOS/XIAP and survivin/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 (2023).

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