80 - Redox Biology of Thiosulfate as a Sulfide Donor in Endothelial Cells

Abstract

Recent reports have revealed that hydrogen sulfide (H 2 S) has emerged as the most recent endogenous gasotransmitter involved many physiological and pathological processes. The pathways involved in the production, consumption, and mechanism of action of H 2 S appear to be sensitive to alterations in the redox stress. Thiosulfate (S 2 O 3 2– ) is one of oxidized products of the sulfide pathway, and has been used extensively and safely to treat calcific uremic arteriopathy (a disease, in part due to calcification of small arteries) in dialysis patients. Yet despite its significance, fundamental questions regarding how thiosulfate and H 2 S interact during redox signaling remain unanswered. In this study, we examined the effect of thiosulfate on hypoxia-induced H 2 S metabolite bioavailability in human umbilical vein endothelial cells (HUVECs). We found that thiosulfate is a low-dose, slow-releasing sulfide donor that utilizes a glutathione-dependent pathway in a time-dependent manner. Also, it was found that thiosulfate reduces HUVECS proliferation treated with vascular endothelial growth factor (VEGF) in normoxic and hypoxic conditions. These results indicate that thiosulfate can contribute to H 2 S signaling under hypoxic conditions through non-enzymatic and enzymatic pathways and that this is a beneficial sulfide donor. Keywords Thiosulfate, sulfide, anti-angiogenic, glutathione, donor