Role of hydrogen sulfide in modulating the life and death of cells

grantor: University of TorontoHydrogen sulfide was found to be more toxic to hippocampal slice cultures than isolated hepatocytes. Chloride ion channel blockers decreased H 2S cytotoxicity suggesting that H2S enters the cells via these channels. Intracellular H2S was formed from cysteine, metabolism as the cystathionine ã-lyase inhibitor propargylglycine prevented cystinedimethylester (CDME) toxicity towards GSH-depleted hepatocytes but not neurons. However the cystathionine ß-synthase inhibitor aminooxyacetate decreased CDME toxicity in neurons but not hepatocytes. H2S toxicity was decreased by ZnCl2 by complexing H2S or accelerating H2S oxidation. H2S also prevented Zn2+:8-hydroxyquinoline toxicity in hepatocytes. ROS scavengers DMSO and catalase, metal chelators neocuproine, TPEN and desferoxamine and endocytosis inhibitors chloroquine and methylamine also decreased Zn2+ hepatoxicity suggesting that zinc displaces Fe/Cu from storage proteins that have been endocytosed in lysosomes. Hydrogen sulfide was also protective against NO and hypoxia induced toxicity in hepatocytes.M.Sc