Sodium trisulfide, a sulfane sulfur donor, stimulates bovine aortic endothelial cell proliferation in culture

Abstract

Reactive sulfur species (RSS) include biological persulfide molecules that protect cells against oxidative stress and heavy metal toxicity. Vascular endothelial cells regulate blood coagulation and fibrinolytic activity, and prevent vascular disorders such as atherosclerosis. We hypothesized that RSS protect vascular endothelial cells not only from nonspecific cell damage but also from specific functional damage through regulation of specific cell functions. In the present study, cultured bovine aortic endothelial cells were treated with sodium trisulfide, a sulfane sulfur donor, and both [ 3 H]thymidine incorporation and effects on cell cycle were analyzed. These results suggest that RSS stimulate vascular endothelial cell proliferation. RSS may reduce the functional cytotoxicity of antiproliferative agents.

Synthesis of Reactive Sulfur Species in Cultured Vascular Endothelial Cells after Exposure to TGF-β1: Induction of Cystathionine γ-Lyase and Cystathionine β-Synthase Expression Mediated by the ALK5-Smad2/3/4 and ALK5-Smad2/3-ATF4 Pathways

“…Previously, we found that transcription of the gene encoding cystathionine γ-lyase (CSE), an RSS-producing enzyme, is induced by copper diethyldithiocarbamate through activation of the ERK1/2, p38 MAPK, and hypoxia-inducible factor-1α/β (HIF-1α/β) pathways in vascular endothelial cells [17]. Additionally, we revealed that fibroblast growth factor-2 (FGF-2) increases intracellular RSS levels by inducing CSE expression through the ERK1/2 pathway in vascular endothelial cells [18]. Furthermore, we recently observed that sodium trisulfide, a sulfane sulfur donor, promotes vascular endothelial cell proliferation [19].…”

Deductive Toxicology and Bioorganometallics

“…14. Intracellular Signal Pathways That Mediate the Induction of CSE and CBS in Vascular Endothelial Cells[91][92][93] Supersulfides (reactive sulfur species) are produced by supersulfide-producing enzymes such as CSE and CBS and promote the proliferation of vascular endothelial cells 88). CSE and CBS are induced by activating the signaling pathways, including TGF-β-activated ALK5-Smad2/3/4 and ALK5-Smad2/3-ATF4; FGF-2-activated ERK1/2 pathway; and Cu10-activated ERK1/2, p38 MAPK, and HIF-1α/1β pathways.…”