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

9803010 Valerio国际研究员奖励计划使美国科学家和工程师能够在国外进行三到二十四个月的研究。该计划的奖励为联合研究提供了机会，并利用独特或互补的设施、专业知识和国外的实验条件。该奖项将支持Luis G. Valerio, Jr.博士与西班牙巴塞罗那自治大学的Xavier Pares博士进行为期12个月的博士后研究访问。本项目拟在氧化应激增强的大鼠肝细胞模型中确定乙醇脱氢酶（ADH）酶作为抗细胞膜脂质过氧化损伤（脂质过氧化）的防御机制的作用。目的是了解ADH酶代谢4-羟基壬烯醛的功能要求，4-羟基壬烯醛是脂质过氧化的主要产物，使用位点定向诱变。PI将使用化学毒理学和分子生物学来进行这项调查。这项研究的发现将提供一个多学科的方法来了解这种酶是如何发挥作用的，以及它的毒理学关系是什么脂质过氧化。主持人Xavier Pares博士是巴塞罗那大学生物化学和分子生物学教授兼系主任。他与瑞典斯德哥尔摩卡罗林斯卡学院的汉斯·约瓦尔博士有密切合作。他们在理解ADH酶的生物学功能和进化起源的基本知识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一员。除了与这两位国际知名的同事一起进行研究外，他还将获得分子生物学、计算机辅助分子建模和酶动力学方面的新技能。＊＊＊

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. ***