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ETHANOL EFFECTS ON VITAMIN TRANSPORT/MITOGENIC SIGNALING

乙醇对维生素运输/有丝分裂信号传导的影响

基本信息

批准号：
3069345
负责人：
GEORGE I HENDERSON
金额：
$ 6.99万
依托单位：
UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
依托单位国家：
美国
项目类别：
财政年份：
1989
资助国家：
美国
起止时间：
1989-09-29 至 1994-08-31
项目状态：
已结题

项目摘要

The Candidate's immediate and long-term goals reflect a longstanding interest in the effects of ethanol on fetal growth and development. The "immediate" goal is to continue the ethanol related research which is presently funded and ongoing. The latter has evolved from previous work defining the impact of ethanol of fetal development. These essentially completed, more mechanistically oriented studies are now in progress. As should be the case, they have supplied, along with some answers, many question, especially regarding basic mechanisms of fetal cell mitogenic response. "Long-term" goals will b e to focus research on these ,but this will require a relatively stable faculty getting- tenure will be needed and a small (not absent) teaching load. The impacts of this award will be three-fold. First will be to replace the major "soft" money component of my salary, thereby allowing me to 1) continue working on the above projects for their duration and 2) obtain future grants related to these, as the Principal investigator, without salary constraints. Second, I am at a juncture in my career at which I must obtain tenure in order to continue at this institution. A five year salary commitment would greatly enhance the chances of this, allowing continuity of ongoing research. Third, the above salary commitment would release me from the additional teaching load required should further departmental monies be need for my support. Two related research approaches will utilized for the following studies. For the first, the overall goal is an improved understanding of the effects of ethanol on fetal nutrition by determining its effects on placental and fetal cell vitamin transport. Specific aims are 1) to establish the mechanisms of thiamine (B1) and vitamin B6 transport by the term human placenta, 2) to determine the effect of ethanol on these and 30 to undertake concomitant studies with fetal rat hepatocytes in culture. The second is to determine the mechanism(s) by which ethanol impairs fetal cell proliferation. More specifically, the means by which ethanol blocks the epidermal growth factor (EGF) mediated mitogenic responses in rat fetal hepatocytes will be probed. This will focus on the effect of ethanol on EGF receptor tyrosine kinase activity s the site of purturbation of replicative capacity. Inhibition of this process by ethanol may explain, at least in part, the adverse effects of in utero ethanol exposure on the fetus.

候选人的近期和长期目标反映了一个长期的乙醇对胎儿生长发育的影响。的 “近期”目标是继续乙醇相关研究，目前已获资助，正在进行中。后者是从以前的工作发展而来的乙醇对胎儿发育的影响。这些基本上目前正在进行已完成的、更注重机械性的研究。作为应该是这样，他们提供了，沿着一些答案，许多问题，特别是关于胎儿细胞有丝分裂的基本机制反应“长期”目标将B e集中研究这些，但这将需要一个相对稳定的教师获得-终身教职将需要小的时候，也是一个学习的好地方。该奖项的影响将是三方面的。首先，将取代我的工资的主要“软”钱组成部分，从而使我1）继续在上述项目上工作，2）获得作为首席研究员，未来的赠款与这些有关，工资限制。第二，我正处于职业生涯的一个关键时刻，必须获得终身职位才能继续在这个机构工作。五年工资承诺将大大增加这种机会，允许持续不断的研究。第三，上述薪金承诺将我从额外的教学负担中解放出来，我需要部门的资金支持以下研究将采用两种相关的研究方法。首先，总体目标是提高对乙醇对胎儿营养的影响胎盘和胎儿细胞维生素转运。具体目标是：（1）建立硫胺素（B1）和维生素B6的转运机制，术语人胎盘，2）以确定乙醇对这些的影响， 30名参与胎鼠肝细胞的伴随研究，文化第二个是确定乙醇损害胎儿细胞增殖。更具体地说，乙醇阻断表皮生长因子（EGF）介导的促有丝分裂将探测大鼠胎肝细胞中的反应。购买将侧重于乙醇对EGF受体酪氨酸激酶活性的影响复制能力的破坏。抑制这一过程，乙醇可以解释，至少部分，在子宫内的不良影响，酒精对胎儿的影响