Persulfide-Dependent Regulation of Electrophilic Redox Signaling in Neural Cells.

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  • Author(s): Kasamatsu S;Kasamatsu S
  • Source:
    Antioxidants & redox signaling [Antioxid Redox Signal] 2020 Dec 20; Vol. 33 (18), pp. 1320-1331. Date of Electronic Publication: 2020 Jul 21.
  • Publication Type:
    Journal Article; Research Support, Non-U.S. Gov't
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Mary Ann Liebert, Inc Country of Publication: United States NLM ID: 100888899 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1557-7716 (Electronic) Linking ISSN: 15230864 NLM ISO Abbreviation: Antioxid Redox Signal Subsets: MEDLINE
    • Publication Information:
      Original Publication: Larchmont, NY : Mary Ann Liebert, Inc., 1999-
    • Subject Terms:
    • Abstract:
      Significance: Redox homeostasis is precisely modulated by intricate systems that regulate production, elimination, and metabolism of electrophilic substances (electrophiles) in the nervous system. Since the first report of the endogenous production of reactive persulfide species in cells, such as cysteine persulfides (CysSSH), these reactive species have been a topic of extreme interest in the field of redox biology; persulfides/polysulfides possess unique chemical properties and are involved in multiple cellular functions. Recent Advances: Electrophilic signaling is mainly regulated by endogenous electrophiles that are generated from reactive oxygen species, nitric oxide, and their derivatives during stress responses, as well as by exogenous electrophiles, including compounds in foods and environmental pollutants, such as methylmercury (MeHg). Among diverse electrophiles that are endogenously generated, 8-nitroguanosine 3',5'-cyclic monophosphate (8-nitro-cGMP) possesses unique redox properties, of which the biosynthetic pathway, signaling mechanism, and metabolism in cells have been elucidated. Critical Issues: Persulfides, such as CysSSH, that are endogenously produced are critically involved in 8-nitro-cGMP metabolism. Exposure of neurons to the exogenous neurotoxicant, MeHg, causes severe neurodegeneration via disruption of persulfide-dependent 8-nitro-cGMP metabolism. Future Directions: Accumulating evidence indicates that persulfides are involved in various cellular functions under physiological and pathological conditions. These new aspects of redox biology related to persulfides may be frontiers of cell research, medical and clinical investigations of neurodegenerative diseases, as well as other fields. 8-Nitro-cGMP-mediated signaling and its persulfide-dependent metabolism in cells could, therefore, be potential targets for drug development, which may lead to the discovery of new therapeutic agents for many diseases, including neurodegenerative diseases.
    • Contributed Indexing:
      Keywords: 8-nitro-cGMP; neuron; persulfides; redox signaling
    • Accession Number:
      0 (Reactive Oxygen Species)
      0 (Sulfides)
      0 (persulfides)
      31C4KY9ESH (Nitric Oxide)
    • Publication Date:
      Date Created: 20200616 Date Completed: 20210916 Latest Revision: 20210916
    • Publication Date:
      20240105
    • Accession Number:
      10.1089/ars.2020.8130
    • Accession Number:
      32536194