Hypoxic stress tolerance of the blind subterranean mole rat:: Expression of erythropoietin and hypoxia-inducible factor 1α
Hypoxic stress tolerance of the blind subterranean mole rat:: Expression of erythropoietin and hypoxia-inducible factor 1α
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DOI：
10.1073/pnas.0403540101
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发表时间：
2004-06-29
影响因子：
11.1
通讯作者：
Nevo, E
中科院分区：
文献类型：
--
作者：
Shams, I;Avivi, A;Nevo, E
盲目地下鼹鼠(Spalax，Spalacidae)进化出适应策略，以应对冬季洪水期间在洞穴中达到高潮的低氧。采用实时荧光定量聚合酶链式反应技术，比较了循环红细胞的关键调节因子促红细胞生成素(EPO)和低氧诱导因子1α(HIF-1α)在Spalax大鼠和大白鼠肾脏中的基因表达。我们的结果显示，与Rattus相比，Spalax对不同O-2水平的反应明显更高、更快、更长。(I)在常氧状态下，Spalax和Rattus的肾脏都会产生少量的EPO。6%O-2低氧4h后，Rattus EPO表达最强。在这种情况下，Spalax EPO水平是Rattus的3倍。在10%O-2作用24 h后，Spalax EPO的表达达到最大值，是大鼠的6倍：(Ii)常氧条件下Spalax的HIF-1α水平是大鼠的2倍。Spalax HIF-1α在3%O-2低氧4h后达到最大值，是常氧条件下的2倍，而HIF-1a在所研究的任何条件下均未检测到显著变化；(3)在6%O-2条件下，当家鼠不能存活时，生活在重度淹水土壤中的Spalax galili的EPO和HIF-1α水平高于居住在轻度充气土壤中的Spalax juaei。我们认为EPO和HIF-1α的这种表达模式是Spalax耐缺氧适应策略的重要贡献，Spalax是在4000万年的进化过程中为应对地下低氧应激而进化的。
Blind subterranean mole rats (Spalax, Spalacidae) evolved adaptive strategies to cope with hypoxia that climaxes during winter floods in their burrows. By using real-time PCR, we compared gene expression of erythropoietin (Epo), a key regulator of circulating erythrocytes, and hypoxia-inducible factor 1alpha (HIF-1alpha), Epo expression inducer, in the kidneys of Spalax and white rats, Rattus norvegicus. Our results show significantly higher, quicker, and longer responses to different O-2 levels in Spalax compared with Rattus. (i) In normoxia, both Spalax and Rattus kidneys produce small amounts of Epo. Maximal expression of Rattus Epo is noticed after a 4-h hypoxia at 6% O-2. Under these conditions, Spalax Epo levels are 3-fold higher than in Rattus. After 24 h of 10% O-2, Spalax Epo reaches its maximal expression, remarkably 6-fold higher than the maximum in Rattus; (ii) the HIF-1alpha level in normoxia is 2-fold higher in Spalax than in Rattus. Spalax HIF-1alpha achieves maximal expression after 4-h hypoxia at 3% O-2, a 2-fold increase compared with normoxia, whereas no significant change was detected in Rattus HIF-1a at any of the conditions studied; (iii) at 6% O-2 for 10 h, in which Rattus cannot survive, Epo and HIF-1alpha levels in Spalax galili, living in heavily flooded soils, are higher than in Spalax judaei, residing in light aerated soil. We suggest that this pattern of Epo and HIF-1alpha expression is a substantial contribution to the adaptive strategy of hypoxia tolerance in Spalax, evolved during 40 million years of evolution to cope with underground hypoxic stress.