Differences in tryptophan binding to hepatic nuclei of NZBWF1 and Swiss mice: insight into mechanism of tryptophan's effects.
We have observed that in NZBWF1 mice the affinity for L-tryptophan binding to hepatic nuclei in vitro is markedly less than that of Swiss mice. In vitro binding of [3H]tryptophan to hepatic nuclei from both strains was determined without and with unlabeled L-tryptophan (10(-4) mol/L). The relative specific binding of L-tryptophan to hepatic nuclei in vitro was 60.9 +/- 4.4% for Swiss mice and 35.8 +/- 5.4% (P < 0.01) in NZBWF1 mice. The total specific binding (bound radioactivity/mg nuclear protein) of L-tryptophan to hepatic nuclei in vitro was 74.9% (P < 0.05) lower in NZBWF1 mice than in Swiss mice. Other strains (DBA, SJL and BALB/c) had specific binding affinities similar to that of Swiss mice. Serum and hepatic free tryptophan concentrations and hepatic tryptophan dioxygenase activity in mice that were food-deprived overnight or 1 h after tube-feeding L-tryptophan (20 mg/100 g body weight) were similar in the strains of mice. In vitro [14C] leucine incorporation into protein using hepatic microsomes of mice 1 h after tube-feeding L-tryptophan (20 mg/100 g body weight) revealed a significantly greater (P < 0.05) increase relative to food-deprived controls in Swiss mice (76.8 +/- 19.2%) than the increase in NZBWF1 mice (26.5 +/- 2.6%). Nuclear [14C]-labeled RNA release in vitro was increased 77.2 +/- 18.0% by tube-feeding of L-tryptophan in Swiss but only 7.6 +/- 5.8% (P < 0.02) in NZBWF1 mice. Liver nuclear poly(A)-polymerase and nucleoside triphosphatase activities were variably increased by the administration of L-tryptophan in both strains. In summary, compared with Swiss mice, NZBWF1 mice have a lower specific binding affinity for L-tryptophan by hepatic nuclei, and this alteration may account for the other differences in responses to L-tryptophan by the two strains.
Sidransky
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George Washington University Medical Center, Department of Pathology, Washington, DC 20037, USA.
Verney
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D017766:Acid Anhydride Hydrolases / Q000378:metabolism; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D004750:Enteral Nutrition; D008099:Liver / Q000201:enzymology / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D051379:Mice; D043583:Nucleoside-Triphosphatase; D011062:Polynucleotide Adenylyltransferase / Q000378:metabolism; D014176:Protein Biosynthesis; D012313:RNA / Q000378:metabolism; D014364:Tryptophan / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D014366:Tryptophan Oxygenase / Q000378:metabolism
D012313:RNA; D014364:Tryptophan; D014366:Tryptophan Oxygenase; D011062:Polynucleotide Adenylyltransferase; D017766:Acid Anhydride Hydrolases; D043583:Nucleoside-Triphosphatase