The novel neuromodulator hydrogen sulfide: an endogenous peroxynitrite ‘scavenger’?

Abstract

Hydrogen sulfide (H 2 S) is a well-known cytotoxic gas. Recently it has been shown to stimulate N-methyl-D-aspartate (NMDA) receptors to enhance long-term potentiation suggesting a novel neuromodulatory role in vivo. Endogenous levels of H 2 S in the brain are reported to range between 10 and 160 lM. Considerably lower H 2 S levels are reported in the brains of Alzheimer's disease (AD) patients, where levels of brain protein nitration (probably mediated by peroxynitrite) are markedly increased. Activation of NMDA receptors leads to intracellular tyrosine nitration by peroxynitrite. Because H 2 S and peroxynitrite are important mediators in brain function and disease, we investigated the effects of the H 2 S 'donor', sodium hydrogen sulfide (NaSH) on peroxynitritemediated damage to biomolecules and to cultured human SH-SY5Y cells. H 2 S significantly inhibited peroxynitrite-mediated tyrosine nitration and inactivation of a 1 -antiproteinase to a similar extent to reduced glutathione at each concentration tested (30-250 lM). H 2 S also inhibited peroxynitrite-induced cytotoxicity, intracellular protein nitration and protein oxidation in human neuroblastoma SH-SY5Y cells. These data suggest that H 2 S has the potential to act as an inhibitor of peroxynitrite-mediated processes in vivo and that the potential antioxidant action of H 2 S deserves further study, given that extracellular GSH levels in the brain are very low.

Hydrogen sulfide inhibits homocysteine-induced endoplasmic reticulum stress and neuronal apoptosis in rat hippocampus via upregulation of the BDNF-TrkB pathway

“…Hcy induces accumulation of reactive oxygen species (ROS) and stimulates neurotoxicity [43,44] , whereas H 2 S scavenges ROS and protects neurons against oxidative stress [45][46][47][48] . Furthermore, both elevation of Hcy and decrease of H 2 S are detected in the brains of AD patients [49] .…”

Hydrogen Sulfide Protects the Retina from Light-induced Degeneration by the Modulation of Ca2+ Influx

“…Photoreceptor cell death is an irreversible injury that is caused by various factors, such as reactive oxygen species (ROS) and elevated intracellular concentrations of Ca 2ϩ (40). Because H 2 S protects neurons from oxidative stress (17,18,21), it is possible that H 2 S protects photoreceptor cells from light-induced retinal degeneration. To examine this possibility, we investigated the effect of H 2 S on retinal degeneration caused by exposing the retina to excessive levels of light.…”

“…H 2 S facilitates the nuclear localization of a transcription factor, nuclear factor erythroid 2-related factor 2 (Nrf2), which increases the expression of antioxidants such as thioredoxin and heme-oxygenase1 (20). H 2 S produced by 3MST along with CAT can directly react with several cytotoxic oxidant species in mitochondria to protect cells (18,21).…”

Hydrogen sulfide and inflammation: the good, the bad, the ugly and the promising

“…Overproduction of these reactive intermediates would not only damage the bacteria but would damage surrounding tissue, precipitating a further inflammatory response. Inhibition of 'oxidative stress' by inactivating enzymes or the direct 'scavenging' of the oxidant species would be expected to contribute to the many potential anti-inflammatory effects of H 2 S. In vitro experiments have shown that H 2 S generated from sulfide salts (Na 2 S and NaSH) inhibits cellular damage and intracellular protein oxidation induced by HOCl [77,78], ONOO - [79] and • NO [34,80]. NaSH is also reported to scavenge and/or degrade lipid peroxides [81,82] and inhibit the expression and activity of NAD(P)H oxidase [83,84].…”