Suppression of Fas ligand expression on endothelial cells by arsenite through reactive oxygen species

Chronic exposure to arsenite is associated with vascular disease, such as a rteriosclerosis. However, the cellular mechanisms for vascular disease in r esponse to arsenic are not well known. The present study has demonstrated t hat arsenite not arsenate decreased the Fas ligand (FasL) expression on ECV 304 cells through reactive oxygen species. Incubation of ECV304 cells with arsenite decreased the FasL expression and increased the intracellular pero xide levels. In addition, hydrogen peroxide was found to suppress FasL expr ession in a dose-dependent manner. The antioxidant, N-acetyl-cysteine, bloc ked the suppression of FasL expression in response to arsenite. These data suggested that arsenite initiates endothelium dysfunction, at least partly, by suppressing the FasL expression through activating reactive oxygen spec ies sensitive endothelial cell signaling. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.