Hydrogen sulfide anion regulates redox signaling via electrophile sulfhydration

Nat Chem Biol. 2012 Aug;8(8):714-24. doi: 10.1038/nchembio.1018. Epub 2012 Jul 1.


An emerging aspect of redox signaling is the pathway mediated by electrophilic byproducts, such as nitrated cyclic nucleotide (for example, 8-nitroguanosine 3',5'-cyclic monophosphate (8-nitro-cGMP)) and nitro or keto derivatives of unsaturated fatty acids, generated via reactions of inflammation-related enzymes, reactive oxygen species, nitric oxide and secondary products. Here we report that enzymatically generated hydrogen sulfide anion (HS(-)) regulates the metabolism and signaling actions of various electrophiles. HS(-) reacts with electrophiles, best represented by 8-nitro-cGMP, via direct sulfhydration and modulates cellular redox signaling. The relevance of this reaction is reinforced by the significant 8-nitro-cGMP formation in mouse cardiac tissue after myocardial infarction that is modulated by alterations in HS(-) biosynthesis. Cardiac HS(-), in turn, suppresses electrophile-mediated H-Ras activation and cardiac cell senescence, contributing to the beneficial effects of HS(-) on myocardial infarction-associated heart failure. Thus, this study reveals HS(-)-induced electrophile sulfhydration as a unique mechanism for regulating electrophile-mediated redox signaling.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anions
  • Cell Line
  • Cell Membrane
  • Cyclic GMP / analogs & derivatives
  • Cyclic GMP / chemistry
  • Cyclic GMP / metabolism
  • Gene Expression Regulation
  • Genes, ras / physiology
  • Humans
  • Hydrogen Sulfide / chemistry*
  • Hydrogen Sulfide / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Molecular Structure
  • Myocytes, Cardiac / metabolism
  • Oxidation-Reduction
  • RNA Interference
  • Rats
  • Signal Transduction / physiology*


  • 8-nitroguanosine 3',5'-cyclic monophosphate
  • Anions
  • Cyclic GMP
  • Hydrogen Sulfide