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Arsenic induces oxidant stress and NF-KB activation in cultured aortic endothelial cells.

Authors
Barchowsky-A; Dudek-EJ; Treadwell-MD; Wetterhahn-KE
Source
Free Radic Biol Med 1996 Jan; 21(6):783-790
NIOSHTIC No.
00235476
Abstract
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.
Keywords
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
Contact
Pharmacology and Toxicology Dartmouth Medical School Remsen 7650 Hanover, NH 03755-3835
CODEN
FRBMEH
CAS No.
7440-38-2; 7784-46-5
Publication Date
19960101
Document Type
Journal Article
Funding Amount
76183
Funding Type
Grant
Fiscal Year
1996
NTIS Accession No.
NTIS Price
Identifying No.
Grant-Number-R03-OH-03267
Issue of Publication
6
ISSN
0891-5849
Priority Area
Pulmonary-system-disorders
Source Name
Free Radical Biology and Medicine
State
NH
Performing Organization
Dartmouth College, Hanover, New Hampshire
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