Stomatin-like protein-2 attenuates macrophage pyroptosis and H9c2 cells apoptosis by protecting mitochondrial function

• Published in: Biochemical and biophysical research communications Vol. 636; no. Pt 1; pp. 112 - 120
• Main Authors: Fan, Rui, Jiang, Hongwei, Hu, Yuntao, Xu, Yueyue, Zhou, Yifei, Chen, Ganyi, Liu, Yafeng, Yao, Yiwei, Qin, Wei, Chen, Wen, Huang, Fuhua, Chen, Xin
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 25.12.2022
• Subjects: Animals; Hypoxia - metabolism; Inflammasomes - metabolism; Lipopolysaccharides - metabolism; Macrophage pyroptosis; Macrophages - metabolism; Mice; Mitochondria - metabolism; Mitochondrial dysfunction; mtROS; Nigericin; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism; Pyroptosis; Reactive Oxygen Species - metabolism; SLP-2; Stomatin-like protein-2; STOML2; SLP-2; STOML2; mtROS; Mitochondrial dysfunction; Stomatin-like protein-2; Macrophage pyroptosis
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2022.10.047

Myocytes undergoing hypoxia condition can recruit macrophages and cause pro-inflammation initiation around the injury area. Mitochondrial dysfunction is related to macrophage pyroptosis. Stomatin-like protein-2 (SLP-2) can regulate mitochondrial biogenesis and function. Whether SLP-2 could affect macrophage pyroptosis remains unclear. In this study, bone marrow derived macrophages (BMDMs) were extracted from WT and SLP-2 knocked out mice, then stimulated by LPS/Nigericin. Western blot showed that SLP-2−/− promoted the expression of NLRP3, GSDMD-N, caspase-11 in macrophages, which means the deficiency of SLP-2 augments macrophage pyroptosis. Higher fluorescence intensity of dihydroethidium and TUNEL represented the increased ROS releasing and macrophage programmed death in SLP-2 deficiency groups. The immunofluorescence intensity of MtioTracker Red decreased and that of mitochondrial ROS (mtROS) increased in SLP-2 deletion groups with LPS/Nigericin stimulation, representing the increased mitochondrial damage. The expression level of HIF-1α increased in SLP-2 deletion macrophages with LPS and Nigericin stimulation. The level of Parkin and the ratio of LC3II/I decreased in SLP-2 deficiency macrophages after stimulated by LPS/Nigericin, compared with untreated macrophages. H9c2 cells were cultured in hypoxia condition before being cocultured with macrophage supernatant. The cocultured H9c2 cells were injured due to the serious pyroptosis of SLP-2 deficiency macrophages. According to these results, we suggest that SLP-2 can reduce macrophage pyroptosis and relieve hypoxia H9c2 cells injury through protecting mitochondrial function. •SLP-2 can relieve macrophage pyroptosis by protecting mitochondrial function.•Macrophage pyroptosis augments hypoxia H9c2 cells injury.•HIF-1α takes part in the pathway of pyroptosis.