SEX DIFFERENCES IN HUMAN LYMPHOCYTE Na,K-ATPase AS STUDIED BY LABELED OUABAIN BINDING

Abstract

Lymphocytes Na,K-ATPase is a plasma membrane enzyme that is up-regulated under lymphocytes activation. It is also studied as a model of brain cells Na,K-ATPase. Data about sex-related specificities of the enzyme are not available. The binding of tritium-labelled ouabain to lymphocyte plasma membrane Na,K-ATPase was studied in healthy volunteers of both sexes. The binding interactions were expressed in terms of K(D) and B(Max). The first parameter is related to the affinity of ouabain for the enzyme whereas the second one is related to its density on the cell membrane. Distinct sex-related differences were found. Whereas in males there is a significant direct correlation between the parameters K(D) and B(Max), in females this is not present. However, in females there is a significantly lower K(D) in the 25-37 age range. The latter result probably reflects the expression of subunit variants giving a greater affinity for ouabain. This circumstance may be relevant both to lymphocytes' ability to be activated and to brain function, if one admits that lymphocyte Na,K-ATPase faithfully represents the brain-borne one.

In Vitro Cell Sensitivity to Palytoxin Correlates with High Gene Expression of the Na+/K+-ATPase β2 Subunit Isoform

“…A similar approach was followed to investigate if the variable monocytes sensitivity to PLTX could be affected by healthy volunteers' demographic factors. A previous study already demonstrated an increased affinity of the cardioactive glycoside ouabain for lymphocytes Na + /K + -ATPase in females as compared to males [29]. On the contrary, our results suggest that none of the demographic data (gender, age, and blood group) are related to the variable monocytes sensitivity to PLTX.…”

“…Each of the α and the β subunits present more than one isoform, encoded by different genes, with different tissues expression pattern, as reported by the Model Organism Protein Expression Database (MOPED) [ 27 ]. Moreover, evidence demonstrates different expression patterns of Na + /K + -ATPase subunit isoforms between males and females [ 28 , 29 , 30 ] and it is well known that some isoforms of the α and β subunits own different affinities and sensitivities towards cardioactive glycosides [ 31 , 32 , 33 , 34 , 35 ]. Intriguingly, cardioactive glycosides, such as ouabain, are reported to inhibit PLTX in vitro effects [ 36 , 37 , 38 , 39 , 40 ], being able to modulate PLTX action on the Na + /K + -ATPase in a complex manner: Ouabain acts as a negative allosteric modulator against high PLTX concentrations and as a non-competitive antagonist against low PLTX concentrations [ 41 ].…”

Sex Differences in Brain Injury and Repair in Newborn Infants: Clinical Evidence and Biological Mechanisms

“…The sex difference may have been in part due to differences in the Na+/K+-ATPase responses (70). It has been shown in human peripheral blood lymphocytes that there is a sex difference in the expression and activity of this enzyme (71). In this study the investigators found differential expression of the Na+/K+ ATPase activity in the right and left side of the brain with the differential most pronounced in the female pups.…”