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

• 批准号: 3069344
• 负责人: GEORGE I HENDERSON
• 金额: $ 6.72万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 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
• 来源: https://reporter.nih.gov/project-details/3069344
• 关键词: affinity chromatography; alcoholic beverage consumption; alcoholism /alcohol abuse; apical membrane; autoradiography; basolateral membrane; binding proteins; biological signal transduction; cell growth regulation; embryo /fetus cell /tissue; embryo /fetus drug adverse effect; epidermal growth factor; female; fetal alcohol syndrome; gel electrophoresis; high performance liquid chromatography; human pregnant subject; human tissue; laboratory rat; liver cells; membrane activity; mitogens; mother /embryo /fetus nutrition; phosphorylation; physical separation; placental transfer; prenatal growth disorder; thiamine; thin layer chromatography; tissue /cell culture; vitamin B6

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 对乙醇对胎儿生长发育的影响感兴趣。这个 眼下的目标是继续乙醇相关研究，这是 目前已获得资金并正在进行中。后者是从以前的工作演变而来的 明确酒精对胎儿发育的影响。这些本质上是 已完成的、更多机械化的研究目前正在进行中。AS 应该是这样的，他们提供了许多答案，以及一些答案 问题，尤其是关于胎儿细胞有丝分裂的基本机制 回应。“长期”目标将侧重于这些方面的研究，但这一点 将需要一个相对稳定的教职员工-将需要终身教职 还有少量(不是缺席)的教学负担。 这一奖项将产生三方面的影响。第一个将是替换 我的工资中主要的“软”钱部分，因此我可以1) 在上述项目的持续时间内继续工作，并2)获得 未来与这些有关的赠款，作为首席调查员，没有 工资限制。第二，我正处在我职业生涯的一个转折点 必须获得终身教职才能继续留在这个机构。A五年 工资承诺将极大地增加这种可能性，允许 正在进行的研究的连续性。第三，上述薪金承诺将 将我从所需的额外教学负担中解放出来 我需要各部门的钱来支持我。 下面的研究将采用两种相关的研究方法。 首先，总体目标是更好地理解 测定乙醇对胎儿营养的影响及其对胎儿营养的影响 胎盘和胎儿细胞的维生素运输。具体目标是1)至 建立硫胺素(B1)和维生素B6的转运机制 术语人胎盘，2)以确定乙醇对这些和 30与胎鼠肝细胞进行相伴研究 文化。二是确定乙醇的作用机理(S) 会损害胎儿细胞的增殖。更具体地说，是指 乙醇阻断表皮生长因子(EGF)介导的有丝分裂 将探讨大鼠胎肝细胞的反应。这将集中在 乙醇对表皮生长因子受体酪氨酸激酶活性的影响S 复制能力的紊乱。通过以下方式抑制这一过程 乙醇至少在一定程度上可以解释子宫内酒精的不良影响。 胎儿暴露在酒精中。