TA1 oncofetal rat liver cDNA and putative amino acid permease: Temporal correlation with c-myc during acute CCl4 liver injury and variation of RNA levels in response to amino acids in hepatocyte cultures

TA1 is a rat liver oncofetal cDNA and a member of an emerging family of evo lutionarily conserved molecules with homology to amino acid transporters an d permeases. The aim of these studies was to characterize the regulation an d role of TA1 in acute rat liver injury by examining its relation to regene ration and metabolic stress. Following a single dose of CCl4, TA1 message w as expressed 3-48 h. The major 3.3-kb TA1 transcript correlated temporally with c-myc expression. A novel 2.9-kb TA1 transcript was expressed more var iably 24-48 h. TA1 protein was restricted to hepatocytes in G(0) and G(1) p hases of the cell cycle. Relative to CCl4, a much smaller increase in TA1 w as noted after partial hepatectomy and TA1 preceded the peak of c-myc expre ssion. In vitro TA1 was not induced in hepatocytes by EGF or the acute-phas e cytokines IL-6 and TNF-alpha, but was found to be modulated in response t o amino acid availability. TA1 expression increased in media without argini ne and glutamine and was repressed by total amino acid levels 5-fold over b asal MEM. Together, these results contrast with the constitutive expression observed in transformed cells and suggest an adaptive role for TA1 during liver injury. (C) 1999 Academic Press.