TCCD is a ubiquitous environmental contaminant. Exposure to TCCD result in metabolic, immunologic, reproductive and neoplastic effects in animals. TCDD is a putative human carcinogen and poses a potential risk to human health. We have made the intriguing observation that TCDD up regulates expression of the cytokine inducible isoform of the enzyme nitric oxide synthase and induces nitric oxide biosynthesis by rat hepatic endothelia cells. This is the first demonstration that aryl hydrocarbons regulate an intracellular messenger in the endothelium and provides an important clue on a potential mechanism by which TCCD may alter cellular functioning and induce toxicity. It is our hypothesis that TCDD acts to induce expression of type II no synthase (N0S II) in endothelial cells and that N0 produced in response to TCDD may mediate some of the toxic effects of this contaminant. To test this hypothesis experiments are designed to analyze molecular mechanisms by which TCDD regulates N0 production, and to determine the role of N0 in TCCD-induced tissue injury in rats. These studies will provide information potentially useful for the development of clinical regimens for abrogating TCCD-induced injury in humans. These studies are important and may provide insight into one mechanism by which TCDD induces toxicity.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Program Projects (P01)
Project #
5P01ES006897-04
Application #
6340943
Study Section
Project Start
2000-09-01
Project End
2001-08-31
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
4
Fiscal Year
2000
Total Cost
$156,818
Indirect Cost
Name
University of Medicine & Dentistry of NJ
Department
Type
DUNS #
622146454
City
Piscataway
State
NJ
Country
United States
Zip Code
08854
Jan, Yi-Hua; Richardson, Jason R; Baker, Angela A et al. (2016) Novel approaches to mitigating parathion toxicity: targeting cytochrome P450-mediated metabolism with menadione. Ann N Y Acad Sci 1378:80-86
Kazanecki, Christian C; Kowalski, Aaron J; Ding, Tony et al. (2007) Characterization of anti-osteopontin monoclonal antibodies: Binding sensitivity to post-translational modifications. J Cell Biochem 102:925-35
Kazanecki, Christian C; Uzwiak, Dana J; Denhardt, David T (2007) Control of osteopontin signaling and function by post-translational phosphorylation and protein folding. J Cell Biochem 102:912-24
Gray, Joshua P; Heck, Diane E; Mishin, Vladimir et al. (2007) Paraquat increases cyanide-insensitive respiration in murine lung epithelial cells by activating an NAD(P)H:paraquat oxidoreductase: identification of the enzyme as thioredoxin reductase. J Biol Chem 282:7939-49
Ishijima, Muneaki; Ezura, Yoichi; Tsuji, Kunikazu et al. (2006) Osteopontin is associated with nuclear factor kappaB gene expression during tail-suspension-induced bone loss. Exp Cell Res 312:3075-83
Vetrano, Anna M; Heck, Diane E; Mariano, Thomas M et al. (2005) Characterization of the oxidase activity in mammalian catalase. J Biol Chem 280:35372-81
Martey, Christine A; Vetrano, Anna M; Whittemore, Marilyn S et al. (2005) Inhibition of interferon-gamma signaling by a mercurio-substituted dihydropsoralen in murine keratinocytes. Biochem Pharmacol 70:1726-34
Heck, Diane E; Kagan, Valerian E; Shvedova, Anna A et al. (2005) An epigrammatic (abridged) recounting of the myriad tales of astonishing deeds and dire consequences pertaining to nitric oxide and reactive oxygen species in mitochondria with an ancillary missive concerning the origins of apoptosis. Toxicology 208:259-71
Fakhrzadeh, Ladan; Laskin, Jeffrey D; Gardner, Carol R et al. (2004) Superoxide dismutase-overexpressing mice are resistant to ozone-induced tissue injury and increases in nitric oxide and tumor necrosis factor-alpha. Am J Respir Cell Mol Biol 30:280-7
Heck, Diane E; Gerecke, Donald R; Vetrano, Anna M et al. (2004) Solar ultraviolet radiation as a trigger of cell signal transduction. Toxicol Appl Pharmacol 195:288-97

Showing the most recent 10 out of 77 publications