International Research Fellow Awards: The Role of Mammalian Alcohol Dehydrogenases in the Detoxification of Lipid Peroxidation Products

9803010瓦莱里奥国际研究员奖计划使美国科学家和工程师能够在国外进行3至24个月的研究。该项目的奖项提供了联合研究的机会，并提供了使用国外独特或互补的设施、专业知识和实验条件的机会。该奖项将支持小路易斯·G·瓦莱里奥博士为期12个月的博士后研究访问。与西班牙巴塞罗那自治大学的泽维尔·帕雷斯博士合作。本项目旨在确定乙醇脱氢酶(ADH)酶在氧化应激增强的大鼠肝细胞模型中作为防御细胞膜脂过氧化损伤(脂质过氧化)的作用。目的是了解ADH酶代谢4-羟基壬烯醛的功能需求，4-羟基壬烯醛是利用定点突变产生的脂质过氧化的主要产物。PI将同时使用化学毒理学和分子生物学来进行这项调查。这项研究的结果将提供一个多学科的方法来理解这种酶的功能以及它与脂质过氧化的毒理关系。主持人泽维尔·帕雷斯博士是巴塞罗那大学生物化学和分子生物学系的教授和主任。他与瑞典斯德哥尔摩卡罗林斯卡研究所的汉斯·约恩瓦尔博士密切合作。他们在我们对ADH酶的生物学功能和进化起源的基本知识的理解方面取得了重大进展。瓦莱里奥博士将成为这一多国合作的成员。除了与这两位享誉国际的同事一起做研究外，他还将在分子生物学、计算机辅助分子建模和酶动力学方面获得新的技能。***

9803010 Valerio The International Research Fellow Awards Program enables U.S. scientists and engineers to conduct three to twenty- four months of research abroad. The program's awards provide opportunities for joint research, and the use of unique or complementary facilities, expertise and experimental conditions abroad. This award will support a twelve-month postdoctoral research visit by Dr. Luis G. Valerio, Jr. to work with Dr. Xavier Pares of the Universitat Autonoma de Barcelona in Spain. This project proposes to determine the role of the alcohol dehydrogenases (ADH) enzyme as a defense mechanism against peroxidative damage to cellular membrane lipids (lipid peroxidation) in a rat liver cell model of enhanced oxidative stress. The objective is to understand functional requirements of the ADH enzyme to metabolize 4- hydroxynonenal, a major product of lipid peroxidation using site-directed mutagenesis. The PI will use both chemical toxicology and molecular biology to do this investigation. The findings of this research will provide a multidisciplinary approach to understanding how this enzyme functions and what its toxicological relationship is to lipid peroxidation. The host, Dr. Xavier Pares is Professor and Chair in the Department of Biochemistry and Molecular Biology at the University of Barcelona. He has a close collaboration with Dr. Hans Jornvall of the Karolinska Institute in Stockholm, Sweden. They have made significant progress in the understanding of our basic knowledge of the biological function and evolutionary origins of the ADH enzyme. Dr. Valerio will become a member of this multi-country collaboration. Besides doing research with these two internationally-respected colleagues, he will gain new skills in molecular biology, computer-assisted molecular modeling, and enzyme kinetics. ***