Cold adaptation of cellular sgnalling cascades: The role of the master regulator of oxygen homeostasis HIF-1 (Hypocia inducible factor) in Antarctic fishes

南极鱼类已经进化成高度适应寒冷的表型，包括对O2-运输系统的各种适应。推测冷适应还涉及转录因子HIF-1介导的O2依赖基因表达的改变。对1种温带鱼类和4种冷适应南极鱼类的HIF-1亚基进行测序发现，与哺乳动物或其他非极地鱼类相比，HIF-1亚基的推导序列存在显著差异，这可能反映了转录因子的冷适应，表明极地鱼类的蛋白质功能和/或调节机制经历了不同于哺乳动物的进化。在拟议的项目中，将研究HIF-1在冷适应南极鱼类中的生理意义和分配，以了解这些鱼类是否存在HIF，不同的低氧条件是否可以诱导HIF，以及HIF反应可能介导什么样的生理效应。在第二个目标中，我们将研究冷适应鱼类HIF反应的分子机制。这一部分旨在阐明与温带鱼类和吸热动物(哺乳动物模式生物)相比这一机制的进化变化。这些研究将扩大我们对这一重要的生理调节器的认识，并拓宽我们对重要调控信号级联的冷适应的一般理解。

Antarctic fish have evolved into a highly cold-adapted phenotype, including a variety of adaptations of the O2-transport system. It is hypothesised that cold adaptation also involves modification of O2-dependent gene expression mediated by the transcription factor HIF-1. Sequencing of the hypoxia-inducible subunit HIF-1¿ from one temperate and four cold-adapted Antarctic fishes have detected remarkable differences in the deduced peptide sequences compared with mammals or other non-polar fishes, which might reflect cold adaptation of the transcription factor and suggest that the protein function and/or the regulatory mechanism has undergone a different evolution in polar fishes than in mammals.In the proposed project the physiological importance and assignment of HIF-1 in cold-adapted Antarctic fishes will be studied to know whether there is HIF in these fishes, whether HIF can be induced by different hypoxia conditions and what kind of physiological effects might be mediated by the HIF response. In the second objective the molecular mechanisms regulating the HIF response in cold-adapted fish will be investigated. This part aims to clarify the evolutionary change of this mechanism in comparison to temperate fish and also in comparison to endothermal animals (mammalian model organisms).Together, the proposed studies will extend our knowledge on this important physiological modulator, the master regulator of oxygen homeostasis and broaden our general understanding of cold adaptation of important regulatory signallingcascades.