MOLEC GENETIC & BIOCHEM INVESTIGATION OF THIAMINE TRANS

描述：硫胺素缺乏症[TD]，一种常见的 酒精中毒，在很大程度上促进了 酗酒者和营养不良者的各种器官系统，包括大脑 个人。之前的一些调查工作主要集中在 硫胺素利用酶活性的降低 涉及机械性和对TD的敏感性。对这一问题的理解 导致TD脑损伤的分子事件及其变异性 组织和个人的敏感性不能忽视饮食和 硫胺素的细胞内可利用性。和之间的相互关系 酒精和TD对神经损伤的相对贡献仍然是 澄清了。我们最近的研究表明，一种复杂的、特定类型的细胞 硫胺素及其磷酸化对细胞内库的调节 衍生物，导致了酵母硫胺转运蛋白的克隆，以及 已经指出了硫胺素缺陷的一些后果 摄取系统。硫胺素摄取在这里被定义为运输 硫胺摄取系统。硫胺素摄取在这里被定义为运输 硫胺素进入细胞和胞内室及其转化 硫胺素焦磷酸[TPP]。我们想获得一个更好的 对硫胺素摄取的理解以及摄取和摄取之间的相互作用 饮酒。此外，我们对硫胺素如何 酒精摄取及其伴随的摄取改变 有助于组织特异性和个体间的差异 对TD的敏感性。因此，我们提出了分子遗传学和生化学 急、慢性酒精中毒大鼠对硫胺素摄取的研究 TD，以及两种大鼠条件的组合。我们将克隆和 大鼠硫胺素转运体和硫胺素的cDNA序列 焦磷酸激酶[TPK]。针对编码蛋白的抗体将是 获得。克隆和抗体将被用来检测 组织分布和表达的定性和定量研究 转运蛋白和TPK在暴露大鼠中的表达。酒精对人体健康的影响 将检查转运体的生化特性。这些 实验将在近交系和近交系大鼠身上进行，后者 它们对TD有不同的易感性或表现出不同的酒精含量 饮酒喜好。

DESCRIPTION: Thiamine deficiency [TD], a frequent complication of alcoholism, contributes significantly to the development of damage in various organ systems, including the brain, of alcoholics and malnourished individuals. Previous work by a number of investigations has focused on reductions in the activities of thiamine-utilizing enzymes as being involved mechanistically and sensitivity to TD. The understanding of the molecular events leading to TD-induced brain damage and to variable tissue- and individual-sensitivity cannot ignore the dietary and intracellular availability of thiamine. The interrelationship between and the relative contribution of alcohol and TD to neural damage remains to be clarified. Our recent work has indicated a complex, cell-type specific regulation of intracellular pools of thiamine and its phosphorylated derivatives, had led to the cloning of the yeast thiamine transporter, and has indicated some of the consequence of having a defective thiamine uptake system. Thiamine uptake is defined here as the transport of thiamine uptake system. Thiamine uptake is defined here as the transport of thiamine into cells and intracellular compartments and its conversion to thiamine pyrophosphate [TPP]. We would like to obtain a better understanding of thiamine uptake and of the interplay between uptake and alcohol consumption. Additionally, we are interested in how thiamine uptake and the concomitant alterations of uptake due to alcohol exposure contribute to tissue-specific and inter individual differences in sensitivity to TD. Thus, we propose a molecular genetic and biochemical study of thiamine uptake in rats exposed to acute and chronic alcohol, to TD, and to a combination of both rat conditions. We will clone and sequence cDNAs for the rat thiamine transporter and thiamine pyrophosphokinase [TPK]. Antibodies to the encoded proteins will be obtained. The clones and the antibodies will be used to examine the qualitative and quantitative tissue distribution and expression of the transporter and TPK in the exposed rats. The effects of alcohol on the biochemical properties of the transporter will be examined. These experiments will be done on outbred and inbred rat strains, the latter of which are differentially susceptible to TD or show different alcohol drinking preferences.