Resistance of mitochondrial DNA-depleted cells against oxidized low-density lipoprotein-induced macrophage pyroptosis

Yan,Hai; Li,Yunyun; Peng,Xue; Huang,Dake; Gui,Li; Huang,Baojun

doi:10.3892/mmr.2016.5077

Resistance of mitochondrial DNA-depleted cells against oxidized low-density lipoprotein-induced macrophage pyroptosis

Authors:
- Hai Yan
- Yunyun Li
- Xue Peng
- Dake Huang
- Li Gui
- Baojun Huang
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Affiliations: Department of Immunology, School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui 230032, P.R. China, Comprehensive Laboratory, School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui 230032, P.R. China
Published online on: March 31, 2016 https://doi.org/10.3892/mmr.2016.5077
Pages: 4393-4399

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Abstract

Oxidized low-density lipoprotein (Ox-LDL)-induced macrophage pyroptosis is critical in atherosclerosis inflammation and plaque instability. It has been reported that mitochondrial (mt)DNA-depleted (rho0) cells demonstrate resistance to apoptosis. However, little is known about the susceptibility of rho0 cells to Ox-LDL-induced macrophage pyroptosis. Pyroptosis, a caspase-1-dependent programmed cell death, which compromises membrane integrity, cleaves pro-interleukin (IL)‑1β and pro‑IL‑18 into IL‑1β and IL‑18, respectively and releases damage‑associated molecular pattern molecules, is triggered by a variety of stimuli, including Ox‑LDL. In the present study, the expression levels of cleaved caspase‑1 and IL‑1β in Ox‑LDL‑treated J774A.1 rho0 cells were observed to be significantly decreased when compared with Ox‑LDL‑treated J774A.1 normal cells. Furthermore, J774A.1 rho0 cells exhibited a significant reduction in the ratios of dead cells and lactate dehydrogenase release following Ox‑LDL stimulation compared with the J774A.1 normal cells. In addition, the loss of mtDNA did not influence Ox‑LDL‑induced cholesterol accumulation in J774A.1 rho0 cells, which was observed by Oil Red O staining and CHOD‑PAP assay. Finally, J774A.1 rho0 cells exhibited reduced reactive oxygen species (ROS) production and were capable of maintaining the mitochondrial membrane potential following Ox‑LDL treatment. Thus, the results indicate that the loss of mtDNA potentially rendered murine macrophage J774A.1 resistant to Ox‑LDL‑induced pyroptosis by mitigating NACHT, LRR and PYD domains-containing protein 3 inflammasome activation through reducing ROS production. In addition, mtDNA depletion did not interrupt Ox-LDL-induced intracellular lipid accumulation and continued to maintain the mitochondrial membrane potential.

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