Na⁺,K⁺‐ATPase expression during the early phase of liver growth after partial hepatectomy

Abstract

Na+,K+-ATPase expression has been studied in the early phase of liver growth after partial hepatectomy to ascertain whether its increased activity is due to stable effects, involving de novo synthesis and insertion of pumps into the plasma membrane. Na+,K+-ATPase activity progressively increases after partial hepatectomy, reaching a three-fold induction above basal values 12 h after surgery, mRNA amounts of both a~ and/31 subunits are rapidly increased up to two-fold for a~ and nearly three-fold for/31, at 9 and 12 h post-hepatectomy, respectively. This correlates with increased abundance of both subunit proteins. The results prove that the increase of Na+,K+-ATPase activity correlates with higher expression of both subunit proteins and mRNAs, although the characteristics of the induction suggest that some translational and post-translational events may be equally involved in the increased activity of the pump.Key words: Na+,K+-ATPase; Liver regeneration; Gene expression is under complex control, involving transcriptional, translational and post-translational steps. At this stage it is not clear whether the increased Na ÷, K+-ATPase activity occurring in early phases of liver cell proliferation correlates with enhanced expression of their subunits. The aim of this study was to address this issue by monitoring the changes in the amount of mRNA and protein for both subunits, alpha and beta, during the pre-replicative phase of liver growth. Materials and methods Animals and surgeryOvernight fasted male Wistar rats (200~240 g) were used. After pentobarbital anaesthesia (60 mg/kg b.wt. i.p.) rats were laparotomized and partial hepatectomy (approximately 70%) carried out as previously described [8]. A second set of animals that did not undergo hepatectomy but only liver extrusion was used as a group of sham-operated controls. At the indicated times, animals were killed by decapitation and the liver immediately excised and used for the biochemical analysis detailed below. The piece of liver excised during the hepatectomy was also used for these analysis and considered to be a control at zero time.

Differential Expression and Regulation of Nucleoside Transport Systems in Rat Liver Parenchymal and Hepatoma Cells

“…Thus, when liver parenchymal cells are induced to proliferate, they selectively up-regulate this concentrative transport process, SPNT, by a mechanism that is consistent with de novo synthesis of nucleoside carriers, as also shown for other transport systems like those for neutral amino acids 44,45 and the Na,K-ATPase. 46 The increase in the activity of these transport systems that occurs a few hours after partial hepatectomy can also be reproduced in cultured cells. 47 We believe that the significant contribution of the Na ϩ -independent NBTI-sensitive component of transport to the total nucleoside uptake in FAO cells may be interpreted essentially as a consequence of the dedifferentiation or the transformed status of hepatoma cells, rather than a simple adaptation to the proliferative state of these cells.…”

Decreased hepatocyte membrane potential differences and GABAa-β3 expression in human hepatocellular carcinoma

“…Although there is general agreement on the presence of the ␣1 subunit, the status of the ␤1 subunit is less clear. 13,35,36 We were able to detect both ␣1 and ␤1 expression via RT-PCR. However, the pattern of each subunit expression was similar (and certainly not decreased, which would be required to explain HCC depolarization relative to adjacent nontumor tissues).…”

“…Also, like the GABAergic system, changes in Na/K ATPase activity and in particular the ␣1 and perhaps ␤1 subunits have been described in association with changes in hepatocyte proliferative activity. [10][11][12][13][14] The objectives of this study were to (1) document PD levels in HCC and adjacent nontumor tissues, (2) describe the nature and extent of GABA receptor and Na/K ATPase expression in these tissues, and (3) determine what impact enhanced GABA A receptor expression has on malignant hepatocyte growth in vivo.…”

Increased Hepatic Na,K-ATPase Activity during Hepatic Regeneration Is Associated with Induction of the β1-Subunit and Expression on the Bile Canalicular Domain

“…During hepatic regeneration, Na,K-ATPase activity has been reported to be increased in association with both increased ␤ 1 -subunit mRNA and liver plasma membrane fluidity (26 -31), while ␣ 1 -subunit mRNA and protein were either not altered or increased (12,30,32). To examine the possible importance of ␤-subunit induction and membrane lipid fluidity in the regulation of hepatic Na,K-ATPase, we measured the time course of changes in Na,K-ATPase activity, membrane lipid composition and fluidity, and protein expression in liver plasma membrane subfractions.…”