Abstract
Ischemia-reperfusion (I-R) injury causes several diseases, including acute kidney injury. Hibernating mammals survive periods of torpor with a marked drop in tissue perfusion, interspersed with periods of arousal, and consequently I-R injury. In the present study, sensitivity to anoxia and/or reoxygenation and alterations in cellular ATP and homeostasis of the two most energy consuming processes, protein translation and Na+-K+-ATPase function, were evaluated in renal proximal tubular epithelial cells of mouse or native hibernator hamster origin. Compared with the mouse cells, the hamster cells were less sensitive to anoxia and reoxygenation and ATP was preserved under anoxia. Anoxia triggered mechanisms that suppress protein translation in both species. However, under anoxia, the activity of ATPase, which is mostly attributed to Na+-K+-ATPase function, remained stable in the hamster cells but decreased in the mouse cells. In normoxia, ATPase activity in hamster cells was considerably lower than that in mouse cells. As the Na+-K+-ATPase pump preserves the ion gradient against passive leakage through ion channels, the lower energy demand for the function of this pump in hamster cells may indicate less ion leakage due to fewer ion channels. In accordance with this hypothesis, ouabain-treated hamster cells had a higher survival rate than mouse cells, indicating fewer ion channels and consequently slower deregulation of intracellular ion concentration and cell death due to Na+-K+-ATPase inhibition. Therefore, it is likely that the conserved energy from the suppression of protein translation is adequate enough to support the lower energy demand for Na+-K+-ATPase function and cell survival of hamster cells under anoxia. Clarifying how cells of a native hibernator manage energy under warm I-R may reveal novel and possible clinically applicable pathways for preventing I-R injury.