EFFECT OF PRENATAL ALCOHOL EXPOSURE ON GAMMA-GTP

产前酒精暴露对 GAMMA-GTP 的影响

• 批准号: 3877445
• 负责人: EDWARD REYES
• 金额: --
• 依托单位: UNIVERSITY OF NEW MEXICO
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3877445
• 关键词: alcoholic beverage consumption; brain metabolism; cerebellum; concanavalin A; enzyme mechanism; fetal alcohol syndrome; gamma aminobutyrate; glutamyltransferase; glutathione; heart transplantation; hippocampus; isozymes; laboratory rat; liver metabolism; newborn animals; serum

Several studies have demonstrated that alcoholics, as well as problem drinkers, have higher than normal serum levels of gamma- glutamyl transpeptidase (gamma-GTP). Animal models of chronic drinkers have been shown to have elevated levels of gamma-glutamyl transpeptidase in several brain areas. Rats born to mothers which received 35% of their caloric intake in the form of alcohol, both during gestation and lactation were found to have higher levels of gamma-glutamyl transpeptidase in brain and liver than their controls. Additionally, the offspring of the alcohol treated mothers exhibited many of the dysmorphic characteristics seen if Fetal Alcohol Syndrome. Although the role of gamma-GTP in brain has not been clarified, evidence suggests that the enzyme may be involved in determining an individual's sensitivity to alcohol and in some forms of mental retardation. The membrane-bound enzyme is a vital part of the gamma-glutamyl cycle, which accounts for the turnover of glutathione (GSH). The gamma-glutamyl cycle is involved in the synthesis and degradation of GSH and involves transport of GSH out of cells and gamma-glutamyl amino acids into cells. An increase in gamma-GTP activity, such as is seen following alcohol treatment, may be a mechanism by which concentrations of GABA, an inhibitory neurotransmitter, may be increased. It may also produce an increased turnover of GSH. An increase in gamma-GTP activity may be a reflection of the animal's attempt to increase glutathione synthesis to protect itself against the toxic effects of drugs, free radicals and reactive oxygen intermediates. The present study is undertaken to determine the effects of the maternal administration of alcohol on brain, liver and serum gamma-GTP in neonatal rats. Glutathione and GABA levels in brian will also be measured. We will examine the effects of the maternal administration of alcohol on the ontogenesis of the enzyme and will determine whether the biochemical properties of gamma-GTP have been altered. We will measure gamma-GTP activity in brains of pups from gestational age 16 days, to 120 days of age. Female Wistar rats will be bred to adult males and placed on a liquid diet containing alcohol or an isocalorie equivalent amount of carbohydrate in the from of dextrin, starting on day one of gestation. Although there have been many studies involved with determining the effects of the in utero administration of alcohol, most have not given alcohol to the pregnant mothers until after the first 8 days of gestation. We intend to administer alcohol this critical period of development.

一些研究表明，酗酒者，以及 问题饮酒者，有高于正常水平的伽马- 谷氨酰转肽酶（γ-GTP）。 慢性胰腺炎动物模型 饮酒者的γ-谷氨酰水平升高 转肽酶在几个大脑区域。 母鼠所生的老鼠 35%的热量摄入是以酒精的形式获得的， 在妊娠期和哺乳期， γ-谷氨酰转肽酶在大脑和肝脏比他们的 对照 此外，酒精处理的后代 母亲表现出许多畸形特征， 胎儿酒精综合征。 虽然γ-GTP在脑中的作用 尚未澄清，有证据表明，酶可能是 参与确定个人对酒精的敏感性， 在某些形式的智力迟钝。 膜结合酶是 是γ-谷氨酰循环的重要组成部分， 谷胱甘肽（GSH）周转率。 γ-谷氨酰循环是 参与GSH的合成和降解， GSH转运出细胞和γ-谷氨酰氨基酸进入 细胞 γ-GTP活性的增加，例如 酒精治疗后，可能是一种机制， 浓度的GABA，一种抑制性神经递质，可能是 增加 它也可以产生GSH的营业额增加。 一个 γ-GTP活性的增加可能是动物 试图增加谷胱甘肽的合成，以保护自己免受 药物、自由基和活性氧的毒性作用 中间体的 本研究旨在确定 母亲服用酒精对大脑、肝脏、 和新生大鼠血清γ-GTP。 谷氨酸和GABA水平 在布赖恩也将被衡量。 我们将研究的影响， 母体给予酒精对酶的个体发育的影响 并将决定γ-GTP的生化特性 被篡改了 我们将测量大脑中γ-GTP的活性 从胎龄16天到120天。 女性 将Wistar大鼠培育成成年雄性，并给予流质饮食 含有酒精或等热量当量的 糊精形式的碳水化合物，从 怀孕 虽然有很多研究涉及到 确定子宫内给予酒精的影响， 大多数人直到怀孕后才给孕妇喝酒 怀孕的前8天 我们打算在这段时间内 发展的关键时期。