Interleukin‐2‐dependent regulation of Na/K pump in human lymphocytes

Abstract

The present study provides the first evidence that the abundance of catalytic a1-subunit of Na,K-ATPase increases in the course of T cell blast transformation. Immunodepressant cyclosporin A at anti-proliferative doses diminished the induction of a1 protein in activated lymphocytes. Furthermore, in competent T cells, IL-2 increases both the transport activity of Na/K pump and the content of Na,K-ATPase a1 protein in a timedependent manner. A correlation was found between the longterm elevation in ouabain-sensitive Rb influxes and the increase in a1 protein content in late activated T cells. These results suggest that (1) the increased expression of Na,K-ATPase proteins underlie the cell cycle-dependent upregulation of ion pump during T cell transformation, and (2) IL-2 is involved in the regulated expression of Na,K-ATPase in human lymphocytes.

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

“…This increase is accompanied by an increase in α 1 subunit content (Marakhova et al, 2005). The subunit composition of the enzyme and in particular the type of α subunit confer different sensitivity to ouabain (Sweadner, 1989).…”

“…The cation pump rate of Na,K-ATPase increases in activated human blood lymphocytes (Vereninov et al, 1993;Buttgereit et al, 2000;Marakhova et al, 2005). This increase is accompanied by an increase in α 1 subunit content (Marakhova et al, 2005).…”

“…However, this process is of importance for other cell types as well (Hille & Catterall, 1999;Kaplan, 2002). In lymphocytes, up regulation of transport activity of Na/K pump accompanies their activation (Vereninov et al, 1993;Buttgereit et al, 2000;Marakhova et al, 2005). Human lymphocyte Na,K-ATPase has been proposed and used as a viable model of its brain counterpart, in order to study the status Int J Neurosci Downloaded from informahealthcare.com by QUT Queensland University of Tech on 11/01/14…”

Long-term regulation of Na,K-ATPase pump during T-cell proliferation

“…Indeed, our recent investigations revealed that after the initial rise in Na i in response to PHA, Na i remained stable and did not increase during later transition of resting cell to proliferation [22]. In addition, in the late stimulated HBLs, a monensin-induced rise in Na i increases significantly the ouabain-sensitive Rb influx, thus indicating that the pump remains capable of increasing its transport activity in response to elevated Na i [21]. In contrast to rapid pump stimulation, a permanent increase in ouabaininhibitable K transport is always accompanied by a parallel increase in the ouabain binding.…”

“…In our preliminary study, we reported that in activated human lymphocytes, the increased pumping was associated with the increased expression of Na,K-ATPase α1-subunit in the course of G 0 /G 1 /S transition [21]. To elucidate further the underlying mechanisms of the Na,K-ATPase pump regulation during mitogenesis, we have studied pump-mediated ion fluxes, [ 3 H]ouabain binding, and expression of Na,K-ATPase both at protein and mRNA levels in human blood lymphocytes (HBLs).…”