Osmolyte regulation by TonEBP/NFAT5 during anoxia-recovery and dehydration–rehydration stresses in the freeze-tolerant wood frog (Rana sylvatica)

The wood frog, Rana sylvatica, tolerates freezing as a means of winter survival. Freezing is considered to be an ischemic/anoxic event in which oxygen delivery is significantly impaired. In addition, cellular dehydration occurs during freezing because water is lost to extracellular compartments in order to promote freezing. In order to prevent severe cell shrinkage and cell death, it is important for the wood frog to have adaptive mechanisms for osmoregulation. One important mechanism of cellular osmoregulation occurs through the cellular uptake/production of organic osmolytes like sorbitol, betaine, and myo-inositol. Betaine and myo-inositol are transported by the proteins BGT-1 and SMIT, respectively. Sorbitol on the other hand, is synthesized inside the cell by the enzyme aldose reductase. These three proteins are regulated at the transcriptional level by the transcription factor, NFAT5/TonEBP. Therefore, the objective of this study was to elucidate the role of NFAT5/TonEBP in regulating BGT-1, SMIT, and aldose reductase, during dehydration and anoxia in the wood frog muscle, liver, and kidney tissues