Arsenic induces oxidant stress and NF-KB activation in cultured aortic endothelial cells.
Barchowsky-A; Dudek-EJ; Treadwell-MD; Wetterhahn-KE
Free Radic Biol Med 1996 Jan; 21(6):783-790
A study was conducted examining the effects of arsenic (7440382) on endothelial cells. DNA synthesis, intracellular thiol levels, intracellular oxidant formation, and nuclear activation and translocation of transacting factors were analyzed in second passage porcine vascular endothelial cells incubated with sodium-arsenite (7784465). DNA synthesis was increased by low levels of arsenite and unaffected or inhibited by high levels. Intracellular oxidant formation was induced by arsenite in concentrations up to 5 micromolar without affecting intracellular thiol levels. Arsenite induced oxidant formation was completely inhibited following pretreatment of the cells with dimethylfumarate (DMF) or N- acetylcysteine (NAC) which increased intracellular thiol levels. The nuclear content of proteins binding to kappaB consensus sequences was increased by 2.0 micromolar arsenite. The majority of proteins binding consensus kappaB sequences in arsenite or oxidant treated cells were p65/p50 heterodimers. Arsenite induced NF-kappaB binding was significantly reduced by NAC and DMF. The authors conclude that activation of oxidant sensitive endothelial cell signaling is involved in the initiation of arsenite induced vascular dysfunction.
NIOSH-Publication; NIOSH-Grant; Pulmonary-system-disorders; Blood-vessels; Toxic-effects; Arsenites; Arsenic-compounds; Oxidative-enzymes; Oxidative-processes; Free-radicals; Mammalian-cells; Dose-response; Cardiovascular-system-disease; In-vitro-study
Pharmacology and Toxicology Dartmouth Medical School Remsen 7650 Hanover, NH 03755-3835
Free Radical Biology and Medicine
Dartmouth College, Hanover, New Hampshire