NICKEL AND HOMOCYSTEINE RESPONSIVE GENE CHARACTERIZATION
NICKEL AND HOMOCYSTEINE RESPONSIVE GENE CHARACTERIZATION
批准号:
6178301
负责人:
JESSICA E SUTHERLAND
金额:
$3.51万
依托单位国家:
美国
项目类别:
财政年份:
2000
资助国家:
美国
项目状态:
未结题
起止时间:
2000-03-15 至
中文摘要
P43是一种新发现的功能未知的基因,由
培养的人脐静脉内皮细胞同型半胱氨酸
此外,镍还存在于包括人脐静脉内皮细胞在内的各种人类细胞中。
从长远来看,对该基因功能的研究可能会阐明
镍的重要性或毒性所涉及的机制(例如
致癌)。此外,血浆同型半胱氨酸水平高是
在人类中与动脉硬化有关,在大鼠中这种疾病
在服用镍后被观察到。归纳法的研究
镍和同型半胱氨酸对P43的影响可能会增加我们对
这种疾病的发病机制。短期目标是理解
P43基因产物的功能及镍如何诱导该基因
在培养的细胞中。具体目标是:(1)确定效果
P43在细胞功能上的低表达或高表达
反义或强启动子改变p43和p43转录速率
通过Northern印迹分析、免疫细胞化学等方法监测诱导
研究P43蛋白在细胞内的分布,并进行高效液相和薄层色谱分析
检测细胞内同型半胱氨酸代谢;(2)研究
镍或同型半胱氨酸对细胞同型半胱氨酸代谢的影响
正常细胞和转化细胞及镍对细胞的生化影响
同型半胱氨酸代谢通过蛋氨酸的酶分析。
英文摘要
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.
期刊论文(1)
专著(0)
科研奖励(0)
会议论文
DOI:
10.1016/s0027-5107(01)00163-4
发表时间:
2001-08
期刊:
Mutation research
影响因子:
--
作者:
[J. Sutherland;W. Peng;Q. Zhang;M. Costa]
通讯作者:
J. Sutherland;W. Peng;Q. Zhang;M. Costa
NICKEL AND HOMOCYSTEINE RESPONSIVE GENE CHARACTERIZATION
-
批准号:2900400
-
项目类别:
-
资助金额:$3.17万
-
财政年份:1998
-
负责人:JESSICA E SUTHERLAND
-
依托单位:
NICKEL AND HOMOCYSTEINE RESPONSIVE GENE CHARACTERIZATION
-
批准号:2520435
-
项目类别:
-
资助金额:$2.5万
-
财政年份:1998
-
负责人:JESSICA E SUTHERLAND
-
依托单位:
海外基金