CHARACTERIZATION OF OMEGA HYDROXYLASE P450 GENE FAMILY

OMEGA 羟化酶 P450 基因家族的表征

• 批准号: 3243831
• 负责人: James Paul Hardwick
• 金额: $ 13.84万
• 依托单位: NORTHEAST OHIO MEDICAL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-06-01 至 1995-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3243831
• 关键词: DNA binding protein; DNA footprinting; antibody formation; cytochrome P450; eicosanoid metabolism; enzyme activity; enzyme complex; enzyme induction /repression; enzyme mechanism; enzyme structure; enzyme substrate; gene expression; genetic enhancer element; genetic transcription; human tissue; immunocytochemistry; in situ hybridization; isozymes; laboratory rat; monoclonal antibody; omega 3 fatty acid; oxygenases; restriction fragment length polymorphism; transfection; tumor promoters

The long term objective of this research is to determine the health related effects of induction of the Omega fatty acid hydroxylase gene family (P4501V) by hypolipidemic non-genotoxic tumor promoters. The metabolism of fatty acids, cholesterol and eicosanoids, mediators of paracrine and cellular regulation, by P45OIV members suggest that the regulation of this family may be of importance in inborn errors of fatty acid metabolism, hypercholesteremia, and the inflammation process. The present objective of this grant is to (1) define the size and complexity of the human omega fatty acid hydroxylase P-450 gene family (P4501V), (2) determine the substrate specificities of each P-450 member and whether selective isozymes and activities are polymorphic in the human population, and (3) to define and characterize those genetic elements which function in the expression of these genes and are responsive to induction by tumor promoting hypolipideamic drugs, peroxisomal proliferating agents as well as during starvation and diabetes. Data from these studies will provide insight into the mechanisms of transcriptional activation of omega fatty acid metabolizing P4501V gene family by hypolipideamic drugs, as well as during starvation, and drug induced diabetes. Characterization of the substrate catalytic activities of human P4501V gene will help to determine their function in the omega oxidation of fatty acids, prostaglandins and leukotrines. These data will identify the functional roles these P-450s play in fatty acid cholesterol and eicosanoid metabolism. Results may also have their importance in the human population with respect to inborn errors of fatty acid metabolism, the inflammatory response and their functional role during tumor promotion by non-genotoxic peroxisomal proliferating agents.

这项研究的长期目标是确定 ω-脂肪酸羟化酶基因诱导的相关效应 家族（P4501 V）通过降血脂非遗传毒性肿瘤促进剂。的 脂肪酸、胆固醇和类二十烷酸的代谢， 旁分泌和细胞调节，由P45 OIV成员表明， 该家族的调节可能在脂肪肝的先天性缺陷中具有重要意义。 酸代谢、高脂血症和炎症过程。 这项补助金目前的目标是（1）确定规模， 人ω-脂肪酸羟化酶P-450基因家族的复杂性 （2）确定每个P-450成员的底物特异性 以及选择性同工酶和活性在人类中是否具有多态性 群体，以及（3）定义和表征这些遗传元件 其在这些基因的表达中起作用， 促肿瘤降脂药、过氧化物酶体诱导 增殖剂以及在饥饿和糖尿病期间。 这些研究的数据将为深入了解 ω-脂肪酸代谢P4501 V基因的转录激活 家庭的降脂药物，以及在饥饿，药物 诱发糖尿病。底物催化活性的表征 人类P4501 V基因将有助于确定它们在omega中的功能， 氧化脂肪酸、洋地黄素和白三烯。这些数据将 确定这些P-450在脂肪酸胆固醇中发挥的功能作用 和类花生酸代谢。结果也可能具有其重要性， 人群脂肪酸代谢先天性缺陷， 肿瘤促发过程中炎症反应及其功能作用 非遗传毒性过氧化物酶体增殖剂。