Oxidant-induced activation of protein kinase A: from biochemistry to the cardiovascular physiology of a novel 'redox-dead' knock-in mouse

氧化剂诱导的蛋白激酶 A 激活：从生物化学到新型“氧化还原死亡”敲入小鼠的心血管生理学

• 批准号: G1000458/1
• 负责人: Philip Eaton
• 金额: $ 47.46万
• 依托单位: King's College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2010
• 资助国家: 英国
• 起止时间: 2010 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G1000458%2F1
• 关键词: Oxidant; induced; activation; protein; kinase

Free radicals and oxidising chemicals are produced in cells and tissues. Historically these have been primarily associated with disease or dysfunction. However, over the past decade there has been a growing realisation that these species are not always harmful, and in fact they can play important regulatory roles. We have found in preliminary studies that a protein (known as protein kinase A), which is very important for how the heart is regulated is chemically modified by oxidants and this directly activates it. Here we outline studies that will help fully define the importance of this modification and activation of protein kinase A, both in health and in disease. We will utilise many experimental approaches in this work, including generation of a genetically modified mouse that has been altered so that it cannot be oxidised and directly activated by oxidants. The availability of such mice would be an invaluable resource that will allow us to study fully the importance of oxidant-induced protein kinase A activation in cells, tissues, organs and the animal as a whole.

自由基和氧化化学物质在细胞和组织中产生。从历史上看，这些主要与疾病或功能障碍有关。然而，在过去的十年里，人们越来越认识到这些物种并不总是有害的，事实上它们可以发挥重要的调节作用。我们在初步研究中发现，一种对心脏调节非常重要的蛋白质（称为蛋白激酶A）被氧化剂化学修饰，并直接激活它。在这里，我们概述了有助于充分定义这种修饰和激活蛋白激酶A的重要性的研究，无论是在健康还是在疾病中。在这项工作中，我们将利用许多实验方法，包括产生一种基因修饰的小鼠，这种小鼠已经被改变，使其不能被氧化剂氧化和直接激活。这种小鼠的可用性将是一个宝贵的资源，将使我们能够充分研究氧化剂诱导的蛋白激酶A激活在细胞，组织，器官和动物作为一个整体的重要性。