4.5 Article

Environmental Electrophiles: Protein Adducts, Modulation of Redox Signaling, and Interaction with Persulfides/Polysulfides

Journal

CHEMICAL RESEARCH IN TOXICOLOGY
Volume 30, Issue 1, Pages 203-219

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/acs.chemrestox.6b00326

Keywords

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Funding

  1. Ministry of Education, Culture, Sports, Science and Technology of Japan [JP25220103, JP15K18906]
  2. Grants-in-Aid for Scientific Research [17K15489] Funding Source: KAKEN

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Included among the many environmental electrophiles are aromatic hydrocarbon, quinones formed during combustion of gasoline, crotonaldehyde in tobacco smoke, methylmercury accumulated in fish, cadmium contaminated in rice, and acrylamide in baked foods. These electrophiles can modify nucleophilie functions such as cysteine residues in proteins forming adducts and in the process activate cellular redox signal transduction pathways such as kinases and transcription factors. However, higher concentrations of electrophiles disrupt such signaling by nonselective covalent, modification of cellular proteins. Persulfide/polysulfides produced by various enzymes appear to capture environmental electrophiles because of the formation of their sulfur adducts without electrophilicity. We therefore speculate that persulfide/polysulfides are candidates for the regulation of redox signal transduction pathways (e.g., cell survival, cell proliferation, and adaptive response) and toxicity during exposure to environmental electrophiles.

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