Up‐regulation of system A activity in the regenerating rat liver

Abstract

System A activity for neutral amino acid transport, measured as the MeAIB‐sensitive Na+‐dependent l‐alanine uptake, is induced 6 h after partial hepatectomy in plasma membrane vesicles from rat livers. Other Na+‐dependent transporters, like system ASC (MeAIB‐insensitive Na+‐dependent l‐alanine transport) and the nucleoside carrier show similar inductions. Up‐regulation of system A is not explained by changes in the dissipation rate of the Na+ transmembrane gradient, as deduced from uptake measurements performed in the presence of monensin. To determine whether induced system A shared any similarity with the activity found in hepatoma cell lines, we analyzed the N‐ethylmaleimide (NEM) sensitivity of system A in both regenerating and control rat liver plasma membrane vesicles. NEM treatment was equally effective in inhibiting system A in both experimental groups. Thus, during the prereplicative phase of liver growth, a transport activity similar to basal system A is up‐regulated in liver parenchymal cells, by a stable mechanism that does not involve changes in the Na+ transmembrane gradient.

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

“…33 This effect can be reproduced in culture by synchronizing FAO cells and inducing them to proliferate by serum refeeding. 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.…”

ATA2-mediated amino acid uptake following partial hepatectomy is regulated by redistribution to the plasma membrane

“…The up-regulation of System A-mediated amino acid transport following PH [12,26,29] is integral to optimal liver regeneration [14]; however, the role of increased amino acid uptake following PH and liver regeneration has remained elusive. The appearance of two System Alike transport activities early in the liver regeneration process may help explain the difficulty in identifying a specific role for increased amino acid uptake in this model of cell proliferation and growth.…”

“…Following 70% resection of rat liver, this regenerative process is remarkable with the liver regaining its original mass within 7 to 10 days [23]. The early regenerative response is complex and characterized by changes in the ion flux at the hepatocyte membrane [25], changes in signal transduction and immediate early gene expression [10,41], expression of oncofetal proteins [11], increased amino acid uptake [12,26,29], and induction of DNA synthesis [18]. Optimal regeneration has been shown to depend on an adequate supply of nutrients, several hormones, growth factors, and cytokines.…”

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

“…Nevertheless, the hepatocyte undergoes more permanent changes at the plasma membrane able to sustain enhanced solute uptake during the pre-replicative phase of liver regeneration. Induction of system A for neutral amino acid transport is stable in plasma membrane vesicles [3,4] and independent of the Na+-transmembrane gradient [4]. Similarly, the concentrative Na*-dependent nucleoside transport system of liver parenchymal cells shows a stable induction early after partial hepatectomy [5].…”

“…Hepatocyte Na +, K+-ATPase activity is increased after partial hepatectomy [2,6,7], probably as a way to compensate for the metabolic pressure induced by the stable increase of several Na+-coupled solute transporters [4,5]. The activity of the pump…”