Inhibition of system A amino acid transport and hepatocyte proliferation following partial hepatectomy in the rat

✍ Scribed by Thomas L. Freeman; Hao Q. Ngo; Mark E. Mailliard

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 119 KB
• Volume: 30
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.510300212

✦ Synopsis

System A, the sodium-dependent neutral amino acid transport activity, has a 3-fold increase in its initial uptake velocity into hepatocytes following partial hepatectomy (PH) in the rat. The purpose of this study was to examine the effect of inhibition of System A-mediated amino acid transport on hepatocyte proliferation and liver regeneration. We describe the in vivo competitive inhibition of System A activity following PH by the nonmetabolizable, System A-specific substrate, ␣-(methylamino)isobutyric acid (MeAIB). Administration of MeAIB 60 minutes before PH decreased the incorporation of [ 3 H]thymidine into DNA by 45% ؎ 5% and 76% ؎ 17% at 24 and 36 hours, respectively. The readministration of MeAIB every 12 hours further decreased DNA synthesis by 92% ؎ 18% and 82% ؎ 11% at 24 and 36 hours. The recovery of liver mass of rats receiving MeAIB was decreased by 46.4% ؎ 5.1% at 24 hours after PH. In vitro, 5 mmol/L MeAIB inhibited proliferation of primary hepatocytes by 56% ؎ 4% and 61% ؎ 12% 48 hours after incubation with 10% fetal calf serum or epidermal growth factor (5 ng/mL), respectively. Thus, MeAIB inhibition of System A transport activity decreased both in vivo and in vitro inducement of hepatocyte proliferation. Treatment with MeAIB did not significantly change the incorporation of [ 3 H]leucine into total liver protein, but changes in serum amino acids and hepatocyte cell volume were observed, suggesting System A transport activity during hepatocyte proliferation functions primarily to provide amino acids to fuel liver-specific biochemical pathways and to increase cell volume. (HEPATOLOGY 1999;30:437-444.