Role of protein hydoxylation in cellular response to hypoxia 67493

细胞如何“感知”周围氧气的变化一直是生物学的一个中心问题。细胞环境中氧气的增加（高氧）或减少（缺氧）对细胞施加了“压力”，细胞必须对此做出反应。适应细胞环境中氧浓度的变化涉及基因和蛋白质表达的启动。这些过程的控制机制取决于蛋白质结构和功能的氧依赖性修饰。这项由NSERC发现补助金支持的拟议研究将在两个一般领域取得进展。第一个将发现新的蛋白质在培养的哺乳动物细胞，是受氧依赖性翻译后修饰。第二个将进一步表征这些蛋白质在氧应激细胞存活中的作用。重点将是适应缺氧条件。所有生物体都会或多或少地遇到环境氧气的变化。在人类中，适应高海拔和局部缺血（停止向器官和组织的血流，例如在心脏骤停、中风或器官移植期间）需要对缺氧做出反应的能力。

How cells "sense" a change in ambient oxygen has long been a central question in biology. Increases (hyperoxia) or decreases (hypoxia) of oxygen in the cellular milieu impose a "stress" upon cells to which they must respond. Adaptation to changes in oxygen concentration in a cell's environment involves the initiation of gene and protein expression. The mechanism of control of these processes is dependent upon oxygen-dependent modification of protein structure and function. The proposed research supported by this NSERC Discovery Grant will lead to progress in two general areas. The first will uncover novel proteins in cultured mammalian cells that are subject to oxygen-dependent posttranslational modification. The second will be to further characterize the role of these proteins in cellular survival of oxygen stress. The focus will be on adaptation to hypoxic conditions. All organisms encounter changes in ambient oxygen to a greater or lesser extent. In humans, adaptation to high altitudes and ischemia (cessation of blood flow to organs and tissues, such as during cardiac arrest, stroke or organ transplant) requires the ability to respond to hypoxia.