Adaptive regulation of neutral amino acid transport System A in rat H4 hepatoma cells.
Substrate regulation of System A transport activity in rat H4 hepatoma cells is described. The uptake of several amino acids was tested in the presence of system-specific inhibitors. System A activity was increased in a RNA- and protein synthesis-dependent manner by amino acid deprivation of the cells (adaptive regulation), whereas transport by Systems ASC, N, y+, and L was unaffected. Unlike human fibroblasts, the H4 cells did not require serum to exhibit the depression of System A. At cell densities between 88 X 10(3) and 180 X 10(3) cells/cm2, the degree of adaptive regulation was inversely related to cell density. Both transport of AIB and adaptive regulation of System A were nearly abolished if either K+ or Li+ was substituted for Na+ in the medium. The presence of cycloheximide or tunicamycin blocked further increases in starvation-induced activity within 1 hr of addition, suggesting the involvement of a plasma membrane glycoprotein. In contrast, if the medium was supplemented with actinomycin after the stimulation of System A had begun, the activity continued to increase for an additional 2 hr before being slowed by the inhibitor. The contributions of trans-inhibition and repression to the amino acid-induced decay of System A activity were estimated for several representative amino acids. In general, the System A activity in normal rat hepatocytes was much less sensitive to trans-inhibition than the corresponding activity in H4 hepatoma cells. The half-life values for the amino acid-dependent decay of System A ranged from 0.5 to 2.0 hr.
Kilberg
M S
MS
Han
H P
HP
Barber
E F
EF
Chiles
T C
TC
D000222:Adaptation, Physiological; D000596:Amino Acids / Q000172:deficiency / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D001692:Biological Transport; D001769:Blood; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D002452:Cell Count; D002460:Cell Line; D008094:Lithium / Q000502:physiology; D008113:Liver Neoplasms; D008297:Male; D009363:Neoplasm Proteins / Q000096:biosynthesis; D012313:RNA / Q000096:biosynthesis; D051381:Rats; D012964:Sodium / Q000502:physiology
D000596:Amino Acids; D009363:Neoplasm Proteins; D012313:RNA; D008094:Lithium; D012964:Sodium