Activation mechanisms of the Hypoxia Inducible Factor-1a (HIF-1a) and the HIF-Like-Factor

缺氧诱导因子 1a (HIF-1a) 和 HIF 样因子的激活机制

• 批准号: nhmrc : 207820
• 负责人: A/Pr Daniel Peet
• 金额: $ 21.11万
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2002
• 资助国家: 澳大利亚
• 起止时间: 2002-01-01 至 2004-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/activation-mechanisms-hypoxia-like-factor/81601
• 关键词: Activation; mechanisms; Hypoxia; Inducible; Factor

A continual supply of oxygen is essential for normal functioning of the human body. When oxygen levels become limiting, the body attempts to rectify the situation by increasing the number of oxygen carrying red blood cells and promoting development of new blood vessels to increase the blood supply to tissues. Cells also adapt by altering their internal biochemistry and metabolism to decrease energy needs. These changes are the result of a genetic reprogramming within the cells. A major question is how the cells sense they are in a low oxygen environment and by what mechanisms they initiate genetic reprogramming. We are studying two proteins which have the ability to alter activity of genes when cells are stressed by hypoxia (low oxygen), and seek to discover how the proteins switch from latent forms to active forms in response to hypoxia. A greater understanding of the molecular mechanisms involved in the cellular hypoxic response is important to the development of new therapeutics for disease states involving disrupted oxygen flow (eg heart attack and stroke). Drugs which would block the hypoxic induced development of blood vessels could also be extremely beneficial in cancer treatment, as blocking blood supply to growing tumours can result in their starvation and shrinkage.

持续的氧气供应对人体的正常运作是必不可少的。当氧气水平变得有限时，人体试图通过增加携氧红细胞的数量和促进新血管的发展来纠正这种情况，以增加组织的血液供应。细胞还通过改变其内部生化和新陈代谢来适应，以减少能量需求。这些变化是细胞内基因重新编程的结果。一个主要的问题是，细胞如何感觉自己处于低氧环境中，以及它们通过什么机制启动基因重新编程。我们正在研究两种蛋白质，它们能够在细胞受到低氧(低氧)的压力时改变基因的活性，并试图发现这些蛋白质如何在低氧条件下从潜在形式转变为活性形式。更好地了解细胞缺氧反应的分子机制对于开发新的治疗涉及氧流中断的疾病状态(如心脏病发作和中风)非常重要。阻止低氧诱导的血管发育的药物在癌症治疗中也可能非常有益，因为阻止生长中的肿瘤的血液供应可能会导致它们饥饿和萎缩。