title: Hypothiocyanous acid is a potent inhibitor of apoptosis and caspase 3 activation in endothelial cells.
abstract: Hypothiocyanous acid (HOSCN) is a common, thiol-specific oxidant with strong antibacterial activity. It is thought to be nontoxic to mammalian cells, although its ability to specifically target intracellular thiols may potentially cause cellular dysfunction. In this study we demonstrate specific effects of HOSCN on human endothelial cells, with exposure to high concentrations resulting in morphology changes unlike those seen with other oxidants. Effects were time- and dose-dependent and were accompanied by loss of total cell thiols and GSH and by inactivation of glyceraldehyde-3-phosphate dehydrogenase. High-dose exposure was cytotoxic, but lesser doses did not cause cell death, and apoptosis was not initiated by any concentration of HOSCN. In fact, initiation of apoptosis was blocked by minimal HOSCN exposure, with activation of caspase 3 and cleavage of the proenzyme being prevented. This was unlikely to be due to direct oxidation of the caspase 3 active-site cysteine and suggests alternative targeting of the caspase pathway. The survival of endothelial cells when HOSCN is present together with an inducer of apoptosis suggests that HOSCN differs from most other oxidants and could affect endothelial cell survival pathways in a way that may have an impact on vascular function.
authors.affiliation: Free Radical Research Group, Pathology Department, University of Otago at Christchurch, Christchurch 8140, New Zealand. stephanie.bozonet@otago.ac.nz
authors.forename: Stephanie M
authors.initials: SM
authors.lastname: Bozonet
authors.forename: Amy P
authors.initials: AP
authors.lastname: Scott-Thomas
authors.forename: Péter
authors.initials: P
authors.lastname: Nagy
authors.forename: Margreet C M
authors.initials: MC
authors.lastname: Vissers
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D004730:Endothelium, Vascular / Q000473:pathology; D004789:Enzyme Activation / Q000187:drug effects; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000037:antagonists & inhibitors; D006801:Humans; D016877:Oxidants / Q000494:pharmacology*; D010084:Oxidation-Reduction / Q000187:drug effects; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013861:Thiocyanates / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D016877:Oxidants; D013438:Sulfhydryl Compounds; D013861:Thiocyanates; C517667:hypothiocyanous acid; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D053148:Caspase 3