Redox regulation of electrophilic signaling by reactive persulfides in cardiac cells

Free Radic Biol Med. 2017 Aug:109:132-140. doi: 10.1016/j.freeradbiomed.2017.01.024. Epub 2017 Jan 18.

Abstract

Maintaining a redox balance by means of precisely controlled systems that regulate production, and elimination, and metabolism of electrophilic substances (electrophiles) is essential for normal cardiovascular function. Electrophilic signaling is mainly regulated by endogenous electrophiles that are generated from reactive oxygen species, nitric oxide, and the derivative reactive species of nitric oxide during stress responses, as well as by exogenous electrophiles including compounds in foods and environmental pollutants. Among electrophiles formed endogenously, 8-nitroguanosine 3',5'-cyclic monophosphate (8-nitro-cGMP) has unique cell signaling functions, and pathways for its biosynthesis, signaling mechanism, and metabolism in cells have been clarified. Reactive persulfide species such as cysteine persulfides and polysulfides that are endogenously produced in cells are likely to be involved in 8-nitro-cGMP metabolism. These new aspects of redox biology may stimulate innovative and multidisciplinary research in cardiovascular physiology and pathophysiology. In our review, we focus on the redox-dependent regulation of electrophilic signaling via reduction and metabolism of electrophiles by reactive persulfides in cardiac cells, and we include suggestions for a new therapeutic strategy for cardiovascular disease.

Keywords: 8-Nitro-cGMP; Electrophilic signaling; Reactive persulfide species; Reductive stress; Senescence.

Publication types

  • Review

MeSH terms

  • Animals
  • Cardiomyopathies / genetics
  • Cardiomyopathies / metabolism*
  • Cardiomyopathies / pathology
  • Cyclic GMP / analogs & derivatives*
  • Cyclic GMP / metabolism
  • Cysteine / analogs & derivatives
  • Cysteine / metabolism
  • Disulfides / metabolism
  • GTP-Binding Proteins / genetics
  • GTP-Binding Proteins / metabolism*
  • Gene Expression Regulation
  • Humans
  • Myocardium / metabolism
  • Myocardium / pathology
  • Myocytes, Cardiac / metabolism*
  • Myocytes, Cardiac / pathology
  • Nitric Oxide / metabolism
  • Oxidation-Reduction
  • Oxidative Stress
  • Protein Aggregation, Pathological / genetics
  • Protein Aggregation, Pathological / metabolism*
  • Protein Aggregation, Pathological / pathology
  • Reactive Oxygen Species / metabolism*
  • Signal Transduction
  • Sulfides / metabolism

Substances

  • 8-nitroguanosine 3',5'-cyclic monophosphate
  • Disulfides
  • Reactive Oxygen Species
  • Sulfides
  • Nitric Oxide
  • cysteine persulfide
  • polysulfide
  • GTP-Binding Proteins
  • Cyclic GMP
  • Cysteine