PMID- 36332472 OWN - NLM STAT- MEDLINE DCOM- 20221116 LR - 20221208 IS - 1090-2104 (Electronic) IS - 0006-291X (Linking) VI - 636 IP - Pt 1 DP - 2022 Dec 25 TI - Stomatin-like protein-2 attenuates macrophage pyroptosis and H9c2 cells apoptosis by protecting mitochondrial function. PG - 112-120 LID - S0006-291X(22)01441-3 [pii] LID - 10.1016/j.bbrc.2022.10.047 [doi] AB - 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-1alpha 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. CI - Copyright (c) 2022 Elsevier Inc. All rights reserved. FAU - Fan, Rui AU - Fan R AD - School of Medicine, Southeast University, Nanjing, Jiangsu, 210009, China; Department of Thoracic and Cardiovascular Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, 210006, China. FAU - Jiang, Hongwei AU - Jiang H AD - Department of Thoracic and Cardiovascular Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, 210006, China. FAU - Hu, Yuntao AU - Hu Y AD - Department of Thoracic and Cardiovascular Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, 210006, China. FAU - Xu, Yueyue AU - Xu Y AD - Department of Thoracic and Cardiovascular Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, 210006, China. FAU - Zhou, Yifei AU - Zhou Y AD - Department of Thoracic and Cardiovascular Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, 210006, China. FAU - Chen, Ganyi AU - Chen G AD - Department of Thoracic and Cardiovascular Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, 210006, China. FAU - Liu, Yafeng AU - Liu Y AD - Department of Thoracic and Cardiovascular Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, 210006, China. FAU - Yao, Yiwei AU - Yao Y AD - Department of Thoracic and Cardiovascular Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, 210006, China. FAU - Qin, Wei AU - Qin W AD - Department of Thoracic and Cardiovascular Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, 210006, China. FAU - Chen, Wen AU - Chen W AD - Department of Thoracic and Cardiovascular Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, 210006, China. Electronic address: cxacf@163.com. FAU - Huang, Fuhua AU - Huang F AD - Department of Thoracic and Cardiovascular Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, 210006, China. Electronic address: huangfuhua@sina.com. FAU - Chen, Xin AU - Chen X AD - School of Medicine, Southeast University, Nanjing, Jiangsu, 210009, China; Department of Thoracic and Cardiovascular Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, 210006, China. Electronic address: stevecx@njmu.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20221020 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (NLR Family, Pyrin Domain-Containing 3 Protein) RN - 0 (Reactive Oxygen Species) RN - 0 (Lipopolysaccharides) RN - RRU6GY95IS (Nigericin) RN - 0 (Inflammasomes) SB - IM MH - Mice MH - Animals MH - *Pyroptosis MH - *NLR Family, Pyrin Domain-Containing 3 Protein/metabolism MH - Reactive Oxygen Species/metabolism MH - Lipopolysaccharides/metabolism MH - Nigericin MH - Macrophages/metabolism MH - Mitochondria/metabolism MH - Hypoxia/metabolism MH - Inflammasomes/metabolism OTO - NOTNLM OT - Macrophage pyroptosis OT - Mitochondrial dysfunction OT - SLP-2 OT - STOML2 OT - Stomatin-like protein-2 OT - mtROS COIS- Declaration of competing interest There is no conflict of interest regarding the publication of this paper. EDAT- 2022/11/05 06:00 MHDA- 2022/11/18 06:00 CRDT- 2022/11/04 19:23 PHST- 2022/10/01 00:00 [received] PHST- 2022/10/03 00:00 [revised] PHST- 2022/10/12 00:00 [accepted] PHST- 2022/11/05 06:00 [pubmed] PHST- 2022/11/18 06:00 [medline] PHST- 2022/11/04 19:23 [entrez] AID - S0006-291X(22)01441-3 [pii] AID - 10.1016/j.bbrc.2022.10.047 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2022 Dec 25;636(Pt 1):112-120. doi: 10.1016/j.bbrc.2022.10.047. Epub 2022 Oct 20.