Role of HIF and Prolyl-hydroxylase enzymes in ventilatory acclimatisation to hypoxia.

HIF 和脯氨酰羟化酶在通气适应缺氧中的作用。

• 批准号: G1001134/1
• 负责人: Keith Buckler
• 金额: $ 68.54万
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2011
• 资助国家: 英国
• 起止时间: 2011 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G1001134%2F1
• 关键词: Role; HIF; Prolyl; hydroxylase; enzymes

Oxygen is essential for most forms of life. Even brief periods without oxygen can cause serious tissue damage or death. In humans the supply of oxygen to tissues is provided by the coordinated operation of lungs, heart & blood supply. The effectiveness with which the lungs load oxygen into the blood is monitored by oxygen sensors located close to major arteries (arterial chemoreceptors). If the body is subject to low levels of oxygen (hypoxia) for prolonged periods of time these chemoreceptors become progressively more sensitive to the lack of oxygen and promote a sustained increase in breathing. This process, called ventilatory acclimatisation, helps us to adapt to changes in environmental oxygen availability such as occur when we go to altitude. Indeed this is one of a number of adaptations that are essential for anyone attempting the assent of very high mountains. Similar changes also occur in some disease states but under these circumstances the effects of enhanced chemoreceptor activity are not always desirable. Our research therefore seeks to understand the mechanisms responsible for ventilatory acclimatisation. In particular we wish to test the hypothesis that oxygen dependent control of gene expression, a process very similar to that which gives rise to increase in the number of red blood cells in hypoxia, also controls chemoreceptor sensitivity.

氧气对大多数生命形式都是必不可少的。即使是短暂的缺氧也会导致严重的组织损伤或死亡。在人类中，组织的氧气供应是由肺，心脏和血液供应的协调运作提供的。肺部将氧气加载到血液中的有效性由位于主动脉附近的氧气传感器（动脉化学感受器）监测。如果身体长时间处于低水平的氧气（缺氧），这些化学感受器会对缺氧逐渐变得更加敏感，并促进呼吸的持续增加。这一过程被称为“净化性适应”，帮助我们适应环境氧气供应的变化，比如当我们去高海拔地区时发生的变化。事实上，这是许多适应之一，对于任何试图获得高山同意的人来说都是必不可少的。类似的变化也发生在一些疾病状态，但在这些情况下，增强的化学感受器活性的影响并不总是令人满意的。因此，我们的研究旨在了解机制，负责净化驯化。特别是，我们希望测试的假设，即氧依赖性控制基因表达，一个过程非常相似，这引起了在缺氧的红细胞数量的增加，也控制化学感受器的敏感性。