Identification of Skp1 as a target of mercury sulfide for neuroprotection.

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  • Additional Information
    • Source:
      Publisher: Royal Society of Chemistry Country of Publication: England NLM ID: 9610838 Publication Model: Electronic Cited Medium: Internet ISSN: 1364-548X (Electronic) Linking ISSN: 13597345 NLM ISO Abbreviation: Chem Commun (Camb) Subsets: MEDLINE
    • Publication Information:
      Original Publication: Cambridge : Royal Society of Chemistry
    • Subject Terms:
      Mercury*/metabolism ; Mercury Compounds*; Animals ; S-Phase Kinase-Associated Proteins ; Caenorhabditis elegans/metabolism ; Neuroprotection ; Sulfides/metabolism
    • Abstract:
      Mercury sulfide (HgS) exerts extensive biological effects on neuronal function. To investigate the direct target of HgS in neuronal cells, we developed a biotin-tagged HgS probe (bio-HgS) and employed an affinity purification technique to capture its target proteins. Then, we identified S-phase kinase-associated protein 1 (Skp1) as a potential target of HgS. Unexpectedly, we discovered that HgS covalently binds to Skp1 through a "Cys62-HgS-Cys120" mode. Moreover, our findings revealed that HgS inhibits the ubiquitin-protease system through Skp1 to up-regulate SNAP-25 expression, thereby triggering synaptic vesicle exocytosis to regulate locomotion ability in C. elegans . Collectively, our findings may promote a comprehensive interpretation of the pharmacological mechanism of mercury sulfide on neuroprotective function.
    • Accession Number:
      FXS1BY2PGL (Mercury)
      0 (S-Phase Kinase-Associated Proteins)
      ZI0T668SF1 (cinnabar)
      0 (Sulfides)
      0 (Mercury Compounds)
    • Publication Date:
      Date Created: 20240115 Date Completed: 20240202 Latest Revision: 20240202
    • Publication Date:
      20240202
    • Accession Number:
      10.1039/d3cc05141b
    • Accession Number:
      38223951