Tissue hypoxia is a condition that induces calcium influx into living cells. Calcium is a major player in maintaining cell signaling and homeostasis, and mediates the regulation of gene transcription and cell proliferation; however, acute and aggressive calcium influx induced by hypoxia eventually leads to programmed cell death. The blind mole rat, Spalax, is a wild-spread burrowing mammal adapted to hypoxic environments. A tyrosine -to- phenylalanine (F481 in Spalax corresponding to Y485 in human full-length receptor; Y460 in human mature form) substitution is found in the erythropoietin receptor of Spalax and other species, which was previously shown to be strongly involved in the calcium channels activation and subsequent calcium influx. The current work aimed to explore the dynamics of calcium transport across Spalax nonhematopoietic cells' membrane compared to above ground rat and mouse, and the role of the erythropoietin receptor of Spalax in the regulation of calcium influx under hypoxia. We show here that Epo-induced calcium influx in HEK293 cells transfected with Spalax EpoR is significantly lower than that of mouse; in hypoxia this difference was even more pronounced. Western blots confirmed a significant increase of Erk phosphorylation after stimulation with erythropoietin under hypoxia in cells transfected with mouse full length erythropoietin receptor compared to Spalax. Native primary fibroblasts showed lower cytosolic calcium concentrations in Spalax cells when compared to those of rats under normoxic and hypoxic conditions. Spalax EpoR appears to play an important role in preventing deleterious consequences of hypoxia and maintaining cellular homeostasis under stress.
Keywords: Blind mole rat; Calcium influx; EpoR; Hypoxia tolerance; Nannospalax.
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