P43 is a newly discovered gene of unknown function that is induced by homocysteine in cultured human umbilical vein endothelial cells (HUVEC) and also by nickel in a variety of human cell types including HUVEC. In the long term, research on this gene's function may elucidate mechanisms involved in nickel's essentiality or toxicity (e.g. carcinogenesis). In addition, high plasma homocysteine levels are associated with arteriosclerosis in humans and this disease in rats has been observed following nickel administration. Studies of the induction of P43 by nickel and homocysteine may increase our understanding of the pathogenesis of this disorder. The short term goals are to understand the functions of the P43 gene product and how nickel induces the gene in cultured cells.
The specific aims are to (1) determine the effects of under or overexpression of P43 on cellular functions by using antisense or a strong promoter to alter transcription rates of P43 and monitoring induction by Northern blot analysis, immunocytochemistry to study cellular distribution of the P43 protein, and HPLC and TLC to examine intracellular homocysteine metabolism; (2) study the effects of nickel or homocysteine doses on cellular homocysteine metabolism in normal and transformed cells and the biochemical effects of nickel upon homocysteine metabolism via enzymatic assays of methionine.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32ES005822-03
Application #
6178301
Study Section
Special Emphasis Panel (ZRG4-ALTX-4 (02))
Program Officer
Shreffler, Carol K
Project Start
2000-03-15
Project End
Budget Start
2000-03-15
Budget End
2001-02-20
Support Year
3
Fiscal Year
2000
Total Cost
$35,136
Indirect Cost
Name
New York University
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
City
New York
State
NY
Country
United States
Zip Code
10016