Characterization of Sodium–Dependent Amino Acid Transport Activity During Liver Regeneration

Abstract

Liver regeneration occurs after removal of or damage to a portion of the liver; it leads to restoration of the original liver mass. The activities of three sodium-dependent amino acid transporters--system A, system N and system ASC--were determined during a 5-day period of liver regeneration in the rat. Seventy-percent hepatectomy or laparotomy was performed in pairs of rats; these rats' livers were removed at different time points after surgery. Transport activity was determined through measurement of the Na(+)-dependent uptake of tritiated amino acids by isolated hepatic plasma membrane vesicles. System A activity, as measured by the Na(+)-dependent uptake of 2-aminoisobutyric acid, is increased in the regenerating liver 2 to 24 hr after surgery compared with that of controls. Kinetic analysis of 2-(methylamino)isobutyric acid uptake showed a 100% increase in the maximum velocity of system A transport in the hepatectomized animals with no change in the Michaelis constant, suggesting an increase in the number of system A transport proteins in the plasma membrane of regenerating liver. During liver regeneration, no changes were noted in the transport activities of system N and system ASC as measured by the uptake of glutamine and cysteine, respectively, in the presence of 2-(methylamino)isobutyric acid. Our work suggests that system A performs a unique role in the secondary active transport of its substrate neutral amino acids to meet the metabolic demands of regenerating liver.

Oligonucleotide microarray analysis of differential transporter regulation in the regenerating rat liver

“…(ii) upregulation of transporters in liver parenchymal cells may be essential to provide substrates for protein synthesis and other cell functions during regeneration. In the regenerating liver cellular influx of amino acids is increased and its inhibition decreases cell proliferation (8). (iii) ion and osmolyte transporters are determinants of the cellular hydration state which is involved in the regulation of cell signaling, stress response, cell proliferation and cell death (9–11).…”

Ontogeny of the Neutral Amino Acid Transporter SNAT1 in the Developing Rat

“…The importance of System A activity during rapid cell proliferation is illustrated in vivo by the liver, an organ possessing the unique ability to regenerate itself following damage or injury. System A activity has been shown to be increased 3-fold within 10-12 h after partial hepatectomy (Fowler et al 1992). In animals given 2-(methylamino) isobutyric acid (MeAIB, a specific competitive inhibitor of System A), 60 min before a partial hepatectomy, the transport activity of System A was reduced by 39%.…”