Redox regulation of electrophilic signaling by reactive persulfides in cardiac cells

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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.Graphical abstractHighlightsCardiovascular electrophilic signaling is controlled by reactive persulfides.Electrophilic signaling by 8-nitro-cGMP is regulated by reactive persulfides.Long-term exposure to electrophiles may increase the risk for cardiovascular diseases.Reactive persulfides suppress 8-nitro-cGMP-mediated cardiac early senescence.Excessive activation of Nrf2 antioxidant response may cause reductive stress in heart.

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