EFFECTS OF ETHANOL ON GLUCOSE TRANSPORTER EXPRESSION

乙醇对葡萄糖转运蛋白表达的影响

• 批准号: 6362157
• 负责人: JOHN J. CALLACI
• 金额: $ 1.51万
• 依托单位: ROSALIND FRANKLIN UNIV OF MEDICINE & SCI
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-03-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6362157
• 关键词: brain metabolism; cell type; developmental neurobiology; dosage; embryo /fetus culture; embryo /fetus toxicology; ethanol; gel mobility shift assay; gene expression; genetic transcription; glucose metabolism; glucose transport; glucose transporter; laboratory rat; messenger RNA; neurons; newborn animals; northern blottings; posttranscriptional RNA processing; protein isoforms; ribonucleoproteins; transport proteins; western blottings

The developing brain is extremely sensitive to the toxic effects of ethanol, but the mechanisms underlying these effects are not well understood. It is proposed that exposure of the developing brain to ethanol results in the specific regulation of the glucose transporter isoforms GLUT1 and GLUT3. It is also proposed that alterations in glucose transporter gene expression may be regulated in a regional and or cell-type specific manner at transcriptional or posttranscriptional levels. Changes in glucose transport, resulting from changes in the levels of glucose transporter proteins, may have a negative impact on important energy and synthetic pathways, as well as protection from free radicals, in immature brain cells. Studies are proposed which examine these changes in gene expression using an in vivo model to delineate regional and cell type differences and using neuronal cultures to further characterize the effect and possible underlying mechanisms, including effects on transcription, message stability, and altered ribonucleoproteins which influence message stability and translation. The long term prospects of this study are that a thorough understanding of the connection between prenatal alcohol exposure and the manifestations of Fetal Alcohol Syndrome will lead to development of effective treatment strategies to minimize or eliminate impairments.

发育中的大脑对乙醇的毒性作用极为敏感，但这些毒性作用背后的机制尚不清楚。有人提出，发育中的大脑暴露于乙醇导致葡萄糖转运蛋白异构体GLUT1和GLUT3的特异性调节。也有人提出葡萄糖转运蛋白基因表达的改变可能在转录或转录后水平上以区域和/或细胞类型特异性的方式调节。葡萄糖转运蛋白水平的变化导致葡萄糖转运的变化，可能对未成熟脑细胞中重要的能量和合成途径以及自由基的保护产生负面影响。研究建议使用体内模型来描述区域和细胞类型差异，并使用神经元培养来进一步表征影响和可能的潜在机制，包括对转录，信息稳定性和影响信息稳定性和翻译的核糖核蛋白改变的影响。这项研究的长期前景是，彻底了解产前酒精暴露与胎儿酒精综合征表现之间的联系，将导致制定有效的治疗策略，以尽量减少或消除损害。