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Biomedical subjects

H Sidransky

Publications and source records attributed to H Sidransky.

At least 91 records · Page 5Linked to original sources

Effect of tryptophan on polyriboadenylic acid and polyadenylic acid-messenger ribonucleic acid in rat liver.

The administration of tryptophan to fasted rats 1 hour before killing resulted in marked increases in the amounts of hepatic polyriboadenylic acid (poly(A)) and poly(a)-containing-mRNA in the cytoplasm and a shift in hepatic polyribosomes toward heavier aggregates. When animals were treated with cordycepin, or actinomycin D, to both, there was disaggregation of hepatic polyribosomes and inhibition of poly(A) synthesis. Administration of tryptophan to fasted animals pretreated with cordycepin, or actinomycin D, or both induced a shift in hepatic polyribosomes toward heavier aggregates and an increase in in vitro protein synthesis. Fasted rats that received [U-14C] adenosine to prelabel hepatic poly (A) and then were treated with cordycepin, or actinomycin D, or both before tubefeeding tryptophan revealed increased hepatic levels of labeled polyribosomal poly (A) in comparison with controls. Fasted rats that received 14C-orotic acid to prelabel poly (A)-mRNA and then were treated with actinomycin D after 1 hour and with tryptophan along with cycloheximide after 1 1/2 hours revealed marked increases in labeling of hepatic poly (A)-mRNA associated with polyribosomes in comparison with controls. These findings suggest that tryptophan may act to stimulate the transport of poly (A)-containing-mRNA into the cytoplasm of the liver.

Adenosine↗

Effect of tryptophan on hepatic polyribosomal disaggregation due to hypertonic sodium chloride.

The effect of tryptophan on the disaggregation of hepatic polyribosomes and on the inhibition of hepatic protein synthesis in rats due to the administration of hypertonic NaCl solutions was studied. Overnight-fasted rats were given by stomach tube or intraperitoneally hypertonic (6.2 to 10.7 per cent) NaCl alone or with 30 mg. of L-tryptophan and were killed 30 minutes later. The hypertonic NaCl treated rats revealed marked hepatic polyribosomal disaggregation and inhibition of hepatic protein synthesis (in vitro incorporation of 14C-leucine into proteins). Rats that received tryptophan alone or in a complete amino acid mixture in addition to hypertonic NaCl revealed a marked improvement in the patterns of hepatic polyribosomes and an increase in in vitro hepatic protein synthesis over that in hypertonic NaCl treated rats. The incorporation of 14C-orotate in hepatic messenger RNA (peak appearing between the 4 S and 18 S RNA fractions) associated with hepatic polyribosomes was studied. Administration of hypertonic NaCl alone caused a decrease in incorporation into hepatic messenger RNA whereas administration of hypertonic NaCl plus tryptophan caused an increase in incorporation into hepatic messenger RNA. Thus, tryptophan appears to cause an increase in hepatic messenger RNA as well as to prevent to a great extent the hepatic polyribosomal disaggregation and the inhibition of hepatic protein synthesis due to hypertonic NaCl.

Amino Acids↗

Nutritional disturbances of protein metabolism in the liver.

Nutritional disturbances of protein metabolism in the liver are reviewed in relation to feeding experimental animals the following diets: a) purified diets deficient in amino acids; b) amino acid mixtures or single amino acids; c) protein-free (amino acid-free) diets; or d) hypertonic or hypotonic solutions. The effects of tube-feeding the diets or dietary components for days, hours, or minutes on hepatic polyribosomes and protein synthesis are described. Force-feeding a purified diet free of single essential amino acids induces within days morphologic changes resembling those that occur in humans with kwashiorkor, a world-wide nutritional deficiency disease in children. In this kwashiorkor-like model, hepatic protein synthesis and polyribosomal aggregation are increased. Administration of a complete amino acid mixture or tryptophan alone, but no other single amino acid, produces a rapid stimulation (within minutes) of hepatic protein synthesis and polyribosomal aggregation in animals that had been fasted, fed, or treated with hepatotoxic agents. A single tube-feeding of a protein-free (amino acid-free) diet induces within hours an increase in hepatic protein synthesis in fasted animals. Administration of hypertonic solutions rapidly (within minutes) inhibits, while administration of hypotonic solutions rapidly increases, hepatic protein systhesis. These experimental findings are reviewed in terms of how alterations in regulatory controls of hepatic protein synthesis may be influenced by nutritional disturbances. Such information may be of importance in designing and utilizing nutritional approaches in the therapy of liver diseases.

Amino Acids, Essential↗

Initiation factors in protein synthesis by free and membrane-bound polyribosomes of liver and hepatoma.

The activity of initiation factors obtained from free and membrane-bound polyribosomes of liver and of transplantable H5123 hepatoma of rats was investigated by using an assay of protein synthesis in vitro in which poly (U)-directed polyphenylalanine synthesis was measured. Initiation factors of membrane-bound polyribosomes prepared by using the anionic detergent deoxycholate exhibited less activity in incorporating [14C]phenylalanyltRNA into polypetides than did initiation factors of free polyribosomes. However, when membrane-bound polyribosomes were prepared after using the non-ionic detergent Triton X-100, no significant differences in activities in polyphenylalanine synthesis were observed between the initiation factors of free and membrane-bound polyribosomes. These results suggest that Triton X-100 is preferable to deoxycholate in the isolation of of initiation factors from polyribosomes. Initiation factors, prepared by using Triton X-100, of free polyribosomes of hepatoma exhibited greater activity in the stimulation of polyphenylalanine synthesis than did the initiation factors of free or membrane-bound polyribosomes of host livers or of membrane-bound polyribosomes of hepatomas.

Animals↗

Influence of quantity of diet on protein synthesis of rats force-fed a threonine-devoid diet.

The influence of the quantity of diet on protein synthesis of rats force-fed a complete diet or one free of threonine for 3 days. Protein synthesis was studied. The results revealed that rats force-fed an adequate amount (6.5 gm. per day) of threonine-devoid diet demonstrated increased hepatic and cardiac protein synthesis and decreased skeletal muscle and splenic protein synthesis in comparison to the results with rats force-fed the complete diet. In contrast, rats force-fed one-half the quantity (3.25 gm. per day) of the diets revealed no or small differences in protein synthesis of the liver, heart, gastrocnemius muscle, and spleen between the rats force-fed the complete and the threonine-devoid diets, although both of the one-half quantity groups had values which were decreased in comparison to those of rats force-fed the adequate quantity of complete diet. The tube feeding of L-threonine (60 mg.) to rats force-fed one-half the quantity of the complete or threonine-devoid diet on the 4th morning 2 hours before killing did not influence the results of organ protein synthesis. Protein synthesis was studied in vivo by measuring 14C-leucine incorporation into organ proteins and in vitro by measuring 14C-leucine incorporation into proteins by using postmitochondrial supernatants or microsomes of livers. Sucrose density gradients of hepatic polyribosomes were studied and revealed that there were more aggregated polyribosomes in rats force-fed adequate quantities of the experimental diets than in those force-fed the control diets. Rats force-fed one-half quantity of the complete and threonine-devoid diets revealed similar polyribosomal patterns which revealed more disaggregation than those in rats ofrce-fed the adequate quantity of complete diet.

Animals↗