Journal of Bioequivalence & Bioavailability

Abstract

Na/K Pump α3-Isoform-Dependent Cell Hydration Controlling Signaling System Dysfunction as A Primary Mechanism for Carcinogenesis

Sinerik Ayrapetyan, Liana Yeganyan, Gagik Bazikyan, Rafayel Muradyan and Flora Arsenyan

More than 40 years cell over-hydration serves as a diagnostic marker for carcinogenesis. However, the nature of cell volume controlling mechanism dysfunction of which leads to over hydration and abnormal cell proliferation is not clear yet. The individual roles of Na+/K+ pump isoforms having different affinity to ouabain (α1-low, α2-midle and α3-high affinity) in cell hydration of different organs of healthy (H) and sarcoma-180 tumor (ST) carrying (SC) mice were studied. The tissue hydration in all organs in SC animals was higher. The pathology-induced cell hydration was accompanied by increase in α3 receptors affinity to 3H-ouabain in excitable and decrease in non-excitable cells. 10-11 M ouabain leads to dehydration while 10-8 and 10-6 M to hydration in SC mice, including ST. Tissue hydration in H and SC mice has different sensitivity to anti cancer drug-cisplatin (cisPt): in H mice it has organo-specific effects while in SC mice it leads to dehydration in all tissues, including ST. This dehydration was accompanied by increase of receptors’ affinity to ouabain which was more pronounced in case of α3-receptors. At 10-6 M ouabain concentration cisPt has hydration effect on muscles and dehydration effect on non-excitable tissues in both H and SC mice, including ST. Cell hydration is suggested as a universal diagnostic marker for cell pathology. Na+/K+ pump α3 isoform-dependent cell hydration controlling signaling system dysfunction is supposed to be a primary mechanism for generation of carcinogenesis. Endogen ouabain circulating in mammalian blood, by its dehydration effect would have antitumor property, and its deficit would promote carcinogenesis.