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Lin Shuang-Zhe,Wu Wei-Jie,Cheng Yu-Qing,Zhang Jian-Bin,Jiang Dai-Xi,Ren Tian-Yi,Ding Wen-Jin,Liu Mingxi,Chen Yuan-Wen,Fan Jian-Gao 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-
Macrophages are immune cells crucial for host defense and homeostasis maintenance, and their dysregulation is involved in multiple pathological conditions, such as liver fibrosis. The transcriptional regulation in macrophage is indispensable for fine-tuning of macrophage functions, but the details have not been fully elucidated. Prolyl endopeptidase (PREP) is a dipeptidyl peptidase with both proteolytic and non-proteolytic functions. In this study, we found that Prep knockout significantly contributed to transcriptomic alterations in quiescent and M1/M2-polarized bone marrow-derived macrophages (BMDMs), as well as aggravated fibrosis in an experimental nonalcoholic steatohepatitis (NASH) model. Mechanistically, PREP predominantly localized to the macrophage nuclei and functioned as a transcriptional coregulator. Using CUT&Tag and co-immunoprecipitation, we found that PREP was mainly distributed in active cis-regulatory genomic regions and physically interacted with the transcription factor PU.1. Among PREP-regulated downstream genes, genes encoding profibrotic cathepsin B and D were overexpressed in BMDMs and fibrotic liver tissue. Our results indicate that PREP in macrophages functions as a transcriptional coregulator that finely tunes macrophage functions, and plays a protective role against liver fibrosis pathogenesis.
2,5-Hexanedione induces apoptosis via a mitochondriamediated pathway in PC12 cells
Yuan Qi,Shuang-yue Li,Feng-yuan Piao,Zhe-min Wang,Ruo-lin Chen,Shuang Liu,Jing-shun Shen 대한독성 유전단백체 학회 2015 Molecular & cellular toxicology Vol.11 No.1
2,5-Hexanedione (HD) is the main active metabolite of n-hexane and mediates the neurotoxicity of the parent compound. Studies suggested that apoptosis involved in HD neurotoxicity. However, the mechanism of HD-induced neuronal apoptosis remains unknown. To explore its underlying mechanism, we treated PC12 cells with 5, 10 and 20 mM HD for 24 h, respectively. We found that HD induced apoptotic death in PC12 cells in a dose-dependent manner. Moreover, HD down-regulated Bcl-2 expression, up-regulated Bax expression and Bax/Bcl-2 ratio, promoted the disruption of mitochondrial transmembrane potential, induced the release of cytochrome c from mitochondria, and increased the activity of caspase-3 in PC12 cells, which were all the key regulators of intrinsic apoptotic pathway. These results indicate that HD induces apoptosis via a mitochondria- mediated pathway in PC12 cells.