甘油三酯通过激活半胱天冬酶-2 和半胱天冬酶-8 诱导单核细胞死亡导致 DNA 损伤。

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

机构信息

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.

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.

出版信息

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

DOI:10.5483/BMBRep.2022-0201

PMID:36593108

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10068338/

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].

摘要

单核细胞是外周白细胞，在先天免疫中发挥作用。过多的甘油三酯（TG）积累会导致单核细胞死亡，从而损害先天免疫。然而，到目前为止，TG 介导单核细胞死亡的机制尚不清楚。因此，本研究旨在阐明 TG 诱导单核细胞死亡的机制。结果表明，TG 通过激活 caspase-3/7 并促进聚（ADP-核糖）聚合酶（PARP）裂解来诱导单核细胞死亡。此外，TG 诱导 DNA 损伤并激活共济失调毛细血管扩张突变（ATM）/检查点激酶 2 和 ATM 和 Rad3 相关（ATR）/检查点激酶 1 途径，导致细胞死亡。此外，TG 诱导的 DNA 损伤和单核细胞死亡由 caspase-2 和 -8 介导，caspase-8 作为 caspase-2 的上游分子。总之，这些结果表明，TG 诱导的单核细胞死亡是通过 caspase-8/caspase-2/DNA 损伤/效应 caspase/PARP 途径介导的。[BMB 报告 2023;56(3):166-171]。