Arsenite induces expression of a reactive sulfur-producing enzyme cystathionine γ-lyase in cultured vascular endothelial cells

<p>Arsenic is a toxic pollutant ubiquitously present in environment. Chronic arsenic exposure is known to be related to the progression of atherosclerosis. The molecular mechanism underlying the development of arsenic toxicity include the inhibition of enzyme activity and increased production of reactive oxygen species (ROS). Recent reports indicate that reactive sulfur species (RSS) have protective effects against ROS. In this study, we investigated the effect of inorganic arsenic compounds on the expression of RSS-producing enzymes (CSE, CBS, CARS1, CARS2, and MST) in cultured vascular endothelial cells. Arsenite, a trivalent inorganic arsenic compound, did not influence the expression of CBS, CARS1 and MST, whereas decreased the expression of CARS2. In addition, arsenite induced the expression of CSE encoding a cystathionine γ-lyase. Furthermore, arsenate, a pentavalent inorganic arsenic compound, did not influence the mRNA expression of CSE. Therefore, these results indicated that arsenite, but not arsenate, selectively induces the expression of CSE in vascular endothelial cells. Hypoxia inducible factor-1 (HIF-1) is known to be involved in transcriptional regulation of CSE. Induction of mRNA expression of CSE by arsenite was partially diminished by a HIF-1 inhibitor, echinomycin. These results suggest that arsenite induces the expression of CSE via activation of HIF-1 pathway.</p>