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 evolutionarily conserved molecules with homology to amino acid transporters and permeases. The aim of these studies was to characterize the regulation and role of TA1 in acute rat liver injury by examining its relation to regeneration and metabolic stress. Following a single dose of CCl4, TA1 message was 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 variably 24-48 h. TA1 protein was restricted to hepatocytes in G0 and G1 phases of the cell cycle. Relative to CCl4, a much smaller increase in TA1 was noted after partial hepatectomy and TA1 preceded the peak of c-myc expression. In vitro TA1 was not induced in hepatocytes by EGF or the acute-phase cytokines IL-6 and TNF-alpha, but was found to be modulated in response to amino acid availability. TA1 expression increased in media without arginine and glutamine and was repressed by total amino acid levels 5-fold over basal MEM. Together, these results contrast with the constitutive expression observed in transformed cells and suggest an adaptive role for TA1 during liver injury.
Shultz
V D
VD
Department of Medical Oncology, Rhode Island Hospital, Brown University School of Medicine, Providence, Rhode Island, USA.
Campbell
W
W
Karr
S
S
Hixson
D C
DC
Thompson
N L
NL
D026905:Amino Acid Transport Systems; D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D002251:Carbon Tetrachloride; D002470:Cell Survival; D002478:Cells, Cultured; D056486:Chemical and Drug Induced Liver Injury; D016207:Cytokines / Q000494:pharmacology; D018076:DNA, Complementary / Q000378:metabolism*; D016259:Genes, myc / Q000235:genetics*; D006498:Hepatectomy; D007700:Kinetics; D027283:Large Neutral Amino Acid-Transporter 1; D008099:Liver / Q000378:metabolism*; D008107:Liver Diseases / Q000378:metabolism*; D008115:Liver Regeneration; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D026905:Amino Acid Transport Systems; D000596:Amino Acids; D016207:Cytokines; D018076:DNA, Complementary; D027283:Large Neutral Amino Acid-Transporter 1; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D012333:RNA, Messenger; C000632119:Slc7a5 protein, rat; D002251:Carbon Tetrachloride