Hydrogen Sulfide Is a Reversible Inhibitor of the NADH Oxidase Activity of Synaptic Plasma Membranes

Biochem Biophys Res Commun. 2009 Oct 30;388(4):718-22. doi: 10.1016/j.bbrc.2009.08.076. Epub 2009 Aug 18.


Hydrogen sulfide is now accepted as a neuromodulator, which can be involved in neuronal defence against oxidative stress insults in the brain. In this work we show that concentrations of H(2)S within the physiological range reported in the brain produce a reversible inhibition of the NADH oxidase activity and coupled superoxide anion production by synaptic plasma membranes from rat brain. At physiological pH 7 the concentration of H(2)S needed for 50% inhibition of the NADH oxidase activity is 5+/-1 microM, which is within the low range of the reported physiological H(2)S concentrations. Thus, the NADH oxidase activity of the neuronal plasma membrane can act as a sensor of local H(2)S depletion in neurones. H(2)S inhibition of the NADH oxidase activity of the neuronal plasma membrane can be accounted for direct reduction by H(2)S of cytochrome b(5). However, H(2)S fails to afford a significant protection against the inhibition of this activity by peroxynitrite. In conclusion, our results point out that H(2)S is more potent as inhibitor of reactive oxygen species formation than as a sacrificial antioxidant.

MeSH terms

  • Animals
  • Cytoprotection*
  • Hydrogen Sulfide / pharmacology*
  • Multienzyme Complexes / antagonists & inhibitors*
  • NADH, NADPH Oxidoreductases / antagonists & inhibitors*
  • Oxidative Stress / drug effects
  • Peroxynitrous Acid / pharmacology
  • Rats
  • Reactive Oxygen Species / antagonists & inhibitors
  • Synaptic Membranes / enzymology*
  • Synaptosomes / enzymology*


  • Multienzyme Complexes
  • Reactive Oxygen Species
  • Peroxynitrous Acid
  • NADH oxidase
  • NADH, NADPH Oxidoreductases
  • Hydrogen Sulfide