Hypoxic stress tolerance of the blind subterranean mole rat:: Expression of erythropoietin and hypoxia-inducible factor 1α

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.