期刊
ACS CHEMICAL NEUROSCIENCE
卷 13, 期 4, 页码 464-476出版社
AMER CHEMICAL SOC
DOI: 10.1021/acschemneuro.1c00621
关键词
gold nanocluster; microglia; HMGB1; cell death; lipid peroxidation; glutathione; oxidative stress; molecular modeling; QM/MM simulations
资金
- Natural Sciences and Engineering Research [RGPIN 2020-07011]
- McGill University
- project STIM-REI - European Union [KK.01.1.1.01.0003, KK.01.1.1.01]
The purpose of this study is to investigate the effects of small liganded gold nanoclusters (Au(10)SG(10)) on various biomarkers in human microglia. It was found that Au(10)SG(10) led to the loss of mitochondrial metabolic activity, increased lipid peroxidation, and translocation of HMGB1 from the nucleus to the cytosol. Molecular modeling provided insights into the interaction sites between amino acids and Au(10)SG(10). Further studies combining live-cell analyses, biomarker determination, and cell functions could contribute to the development of optimized gold nanoclusters for diagnostic and bioimaging purposes in neuroscience.
The purpose of the current study is to uncover the impact of small liganded gold nanoclusters with 10 gold atoms and 10 glutathione ligands (Au(10)SG(10)) on several biomarkers in human microglia. We established the links connecting the atomically precise structure of Au(10)SG(10) with their properties and changes in several biomolecules under oxidative stress. Au(10)SG(10) caused the loss of mitochondrial metabolic activity, increased lipid peroxidation and translocation of an alarmin molecule, high mobility group box 1 (HMGB1), from the nucleus to the cytosol. Molecular modeling provided an insight into the location of amino acid interaction sites with Au(10)SG(10) and the nature of bonds participating in these interactions. We show that Au(10)SG(10) can bind directly to the defined sites of reduced, oxidized, and acetylated HMGB1. Further studies with similar complementary approaches merging live-cell analyses, determination of biomarkers, and cell functions could lead to optimized gold nanoclusters best suited for diagnostic and bioimaging purposes in neuroscience.
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