Hochachka Peter W, Rupert Jim L
Depts. of Zoology, and Radiology and Sports Medicine Division, University of British Columbia, Vancouver, Canada.
Bioessays. 2003 May;25(5):515-9. doi: 10.1002/bies.10261.
Included in the acute response of lowlanders exposed to reduced oxygen availability is an elevated red blood cell count due to increased erythropoietin (Epo) synthesis. According to current thinking, hypoxia is "sensed" by hydroxylases that permit Hypoxia Inducible Factor 1alpha (HIF-1alpha) to complex with HIF-1beta to form a transcriptional activator (HIF-1) that drives expression of hypoxia-sensitive genes (such as EPO) under hypoxic conditions. In altitude-adapted Andean natives, the Epo hypoxic response may be blunted; however, our data indicate that the DNA sequences of the genes encoding Epo (including the 3' regulatory region) and HIF-1alpha appear to be conserved. Hence, adaptive changes in the Andean hypoxic response are not a consequence of changes in the primary sequence of these proteins or of known transcriptional regulatory domains of EPO. These results suggest that the altered erthropoietic response in Andean natives reflects adaptations in hypoxia sensing, rather than hypoxia response, mechanisms.
低地居民暴露于低氧环境时的急性反应包括，由于促红细胞生成素（Epo）合成增加，红细胞计数升高。根据目前的观点，低氧被羟化酶“感知”，使得缺氧诱导因子1α（HIF-1α）与HIF-1β结合形成转录激活因子（HIF-1），从而在低氧条件下驱动缺氧敏感基因（如EPO）的表达。在适应高原环境的安第斯原住民中，Epo的低氧反应可能会减弱；然而，我们的数据表明，编码Epo的基因（包括3'调控区）和HIF-1α的DNA序列似乎是保守的。因此，安第斯低氧反应的适应性变化并非这些蛋白质一级序列或EPO已知转录调控域发生变化的结果。这些结果表明，安第斯原住民中红细胞生成反应的改变反映了低氧感知机制而非低氧反应机制的适应性变化。
