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Biomedical subjects

H Sidransky

Publications and source records attributed to H Sidransky.

At least 55 records · Page 3Linked to original sources
PubMed1985

Protective effect of tryptophan and cysteine against carbon tetrachloride-induced liver injury.

The effects of the administration of tryptophan and/or cysteine on carbon tetrachloride (CCl4)-induced hepatic injury were investigated. Rats received CCl4 (1 ml/kg ip) followed 6 hr later by tryptophan (300 mg/kg) and/or cysteine (950 mg/kg) via stomach tube and rats were killed after 24 hr. Treatment with tryptophan, cysteine, or both reduced the degree of hepatic necrosis observed histologically. While CCl4 caused polyribosomal disaggregation and decreased [14C]leucine incorporation into liver proteins in vitro and in vivo, treatment with tryptophan, cysteine, or both caused a shift in polyribosomes toward heavier aggregation and protein synthesis was increased. Serum activities of lactic dehydrogenase (LDH), glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, and gamma-glutamyl-transpeptidase were markedly increased after CCl4 alone but after subsequent treatment with cysteine or with tryptophan and cysteine appreciable decreases occurred. Glutathione concentration decreased but total amount remained constant in the livers of CCl4-treated rats while subsequent treatment with cysteine alone or together with tryptophan elevated both levels of glutathione. Using isolated hepatocytes, CCl4 caused decreases in cell viability, in release of LDH, and in [14C]leucine incorporation into protein. Treatment with CCl4 and tryptophan and/or cysteine revealed that cysteine alone or with tryptophan improved cell viability and decreased LDH release of the cells, while tryptophan alone or with cysteine improved protein synthesis. Upon cytologic evaluation, the isolated hepatocytes revealed membrane distortions after CCl4 alone but these were less marked after CCl4 plus tryptophan, cysteine, or both (most improvement). Thus, tryptophan and cysteine act in a beneficial manner against CCl4-induced hepatic injury in the rat.

Animals↗
PubMed1985

Influence of dietary tryptophan on the induction of gamma-glutamyltranspeptidase-positive foci in the livers of rats treated with hepatocarcinogen.

The ingestion of an elevated level (2%) of L-tryptophan (TRP) in a purified diet was investigated to determine whether it would influence the induction of gamma-glutamyltranspeptidase (GGT)-positive foci in the livers of rats exposed to a hepatocarcinogen. Subtotal hepatectomies were performed, and 18 h later, the rats were given injections i.p. of diethylnitrosamine (30 mg/kg). Ten days later, groups of male rats were placed on choline-supplemented (CS), CS + TRP, choline-deficient (CD), or CD + TRP diets for 10 wk. In two separate experiments, the rats fed the CS + TRP diet or the CD diet developed more and larger GGT + foci than did rats fed the CS diet. Rats fed the CD + TRP diet revealed similar changes to those found in rats fed the CD diet. The liver weights of the rats fed the CD or the CD + TRP diet were greater than those of rats fed the CS or the CS + TRP diet. Hepatic GGT activity was somewhat elevated in rats fed the CS + TRP diet and markedly elevated in rats fed the CD or the CD + TRP diet. Hepatic ornithine decarboxylase activity was increased in rats fed the CD + TRP diet. The results suggest that increased dietary tryptophan has a promoting effect on liver carcinogenesis as measured by the induction of GGT + foci in the livers of rats exposed to diethylnitrosamine. A potentiating effect by tryptophan was not observed in the livers of rats fed a CD diet.

Amino Acids↗
PubMed1985

Chemical pathology of diamino acid deficiency: considerations in relation to lysinuric protein intolerance.

Young rats were force-fed a lysine + arginine-devoid diet or a complete diet for 3 days, and selected biochemical and morphologic studies were conducted. Rats force-fed the experimental diet in comparison with those force-fed the control diet for 3 days showed decreased body weight gain, hepatomegaly with periportal fatty liver, pancreatic and splenic atrophy, and enhanced 14C-leucine incorporation into hepatic proteins. Differences in the experimental animals were observed in the free amino acid levels of serum (decreased lysine, arginine, and ornithine) and liver (decreased ornithine), in blood chemistries (decreased levels of ammonia N2, uric acid, cholesterol, protein, albumin, alkaline phosphatase, LDH and SGOT) and in hematologic findings (leukocytopenia and thrombocytopenia after a morning feeding). The experimental findings in young rats force-fed the lysine + arginine-devoid diet were compared with those reported to develop in children with lysinuric protein intolerance (LPI), an autosomal recessive defect in diamino acid transport. Children with LPI as described by others reveal a number of similarities as well as a number of differences in comparison to the findings in the experimental animals. The comparison suggests that some of the pathological manifestations of LPI may be related to a deficiency of diamino acids but others must be due to different alterations in this complex human disease.

Amino Acids↗
PubMed1984

Effect of tryptophan on informosomal and polyribosome-associated messenger RNA in rat liver.

The possible role that informosomal mRNA may play in the stimulation of hepatic protein synthesis induced by the acute administration of tryptophan was investigated. L-tryptophan (30 mg/100 g body weight) tube-fed to rats induced an increase (20%) in the amount of polyribosome-associated poly(A+)mRNA in the liver within 1 hour. On the other hand, the amount of the informosomal poly(A+)- mRNA revealed no significant increase or decrease. The size of the increase in the polyribosome-associated poly(A+)mRNA pool was equal to the entire amount of informosomal poly(A+)mRNA present in the hepatic cells. Therefore it was concluded that the failure to detect a significant decrease in the size of the informosomal mRNA pool indicated that the increase in the polyribosome-associated poly(A+)mRNA must be due to a different mechanism, such as enhanced nuclear-to-cytoplasmic translocation of nuclear poly(A+)mRNA, which had been reported earlier. To determine whether any qualitative or quantitative changes occurred in the RNA sequences along with the increase in poly(A+)mRNA following tryptophan administration, DNA/RNA hybridization studies were conducted by using hepatic polyribosome-associated poly(A+)- mRNA from tryptophan-treated and control rats. Although qualitatively no new species of mRNA were detected in the mRNA from tryptophan-treated rats, kinetic analysis of the hybridization curves indicated that there was a shift or accumulation of hepatic poly(A+)mRNA belonging to the intermediate and possibly the high frequency classes of polyribosome-associated poly(A+)mRNA in the livers of the tryptophan-treated rats.

Animals↗
PubMed1984

Nutritional control of protein synthesis. Studies relating to tryptophan-induced stimulation of nucleocytoplasmic translocation of mRNA in rat liver.

Tryptophan has been demonstrated earlier to induce in the livers of rats and mice a rapid stimulation of polyribosomal aggregation and protein synthesis which has been attributed in part to stimulation of translocation of nuclear mRNA into the cytoplasm. This study was concerned with how tryptophan acts to affect the nuclei, particularly the nuclear membranes, in enhancing the nucleocytoplasmic translocation of mRNA of liver cells of rats fasted overnight. The results reveal that tryptophan rapidly becomes incorporated into proteins and also binds to proteins of hepatic cells, particularly proteins of the nuclear envelopes. In vitro binding of 3H-tryptophan to proteins (trichloroacetic-acid-precipitable) of nuclei and cytosols (when incubated together or separately) of livers of tryptophan-treated (10 minutes) rats is increased in comparison with binding to components of control rats. These findings correlate with the enhanced in vitro release of nuclear RNA and the increased activities of nuclear NTPase and protein phosphokinase of the livers of the experimental rats. Preincubation of hepatic nuclei with concanavalin A prevented the increases in in vitro binding of 3H-tryptophan to nuclear proteins, in prelabeled nuclear RNA release, and in nuclear NTPase activity of livers of the tryptophan-treated rats. The results suggest that tryptophan rapidly binds with hepatic proteins (possibly glycoproteins) associated with the nuclear membrane, leading to an increase in the activities of enzymes involved in phosphorylation and dephosphorylation and in release of nuclear mRNA into the cytoplasm.

Amino Acids↗
PubMed1983

Tryptophan-induced stimulation of hepatic ornithine decarboxylase activity in the rat.

The effect of a single tube feeding of L-tryptophan on hepatic ornithine decarboxylase (ODC) activity in rats was investigated. The levels of ODC activity in the livers of control and experimental rats were assayed in vitro by measuring the release of 14CO2 from DL-[1-14C]ornithine. Single tube feedings of varying levels of L-tryptophan (2.5-30 mg/100 g body wt) to overnight-fasted rats 1 hr before sacrifice exhibited increases in the hepatic ODC activities. L-Tryptophan (30 mg/100 g body wt) tube fed to overnight-fasted rats 1/6 to 12 hr before sacrifice induced hepatic ODC activities which were significantly elevated beginning at 1 hr and peaking at 2 hr (6.5-fold increase over controls). In vitro [14C]leucine incorporation into protein using hepatic microsomes of tryptophan-treated rats was significantly increased at 1 hr in comparison with that of controls. The tryptophan-induced stimulation of hepatic ODC activity was not affected by prior adrenalectomy but was abolished by pretreatment with cycloheximide. These studies demonstrate that a single feeding of L-tryptophan can significantly enhance in the rat the activity of ODC, a key enzyme in the biosynthesis of polyamines.

Adrenalectomy↗
PubMed1983

Effect of tryptophan on enzymes and proteins of hepatic nuclear envelopes of rats.

It has been demonstrated earlier that the administration of tryptophan to fasted animals increased the levels of mRNA in the cytoplasm of the liver by stimulating the translocation of nuclear poly(A)-mRNA into the cytoplasm. Also, tryptophan increased the activity of hepatic nuclear envelope (NE) nucleoside triphosphatase, an enzyme considered to be involved in nucleocytoplasmic translocation of mRNA. In this study, the activities of two other NE-associated enzymes, protein phosphokinase and phosphoprotein phosphohydrolase, also implicated in nuclear RNA transport, were investigated in the livers of rats that received a single tube feeding of tryptophan. The administration of tryptophan to fasted rats 10 minutes before killing increased the hepatic NE activities of both enzymes, protein phosphokinase and phosphoprotein phosphohydrolase. Furthermore, tryptophan administration increased the in vivo incorporation of 3H-leucine into NE proteins (+83%) and into other subcellular fractions (+34 to +43%) of the liver compared with that into corresponding fractions of the control rats. Rats that received 3H-leucine to prelabel hepatic proteins and then were treated with puromycin to inhibit further protein synthesis followed by tube feeding of tryptophan revealed greater radioactivity associated with NE proteins than that in controls. These findings suggest that tryptophan may act to stimulate the transport or availability of proteins to the vicinity of the NE, possibly specific regulatory proteins, such as nucleoside triphosphatase, protein phosphokinase and phosphoprotein phosphohydrolase, which show an increase in activity and may then be responsible for the increase in the rate of nucleocytoplasmic translocation of mRNA.

Animals↗
PubMed1981

Effect of elevated dietary tryptophan on protein synthesis in rat liver.

This study investigated whether rats force-fed for three days an elevated (1%) tryptophan diet compared to a control (0.2% tryptophan) diet had changes in hepatic protein metabolism. Earlier, we showed that a single administration of L-tryptophan to fasted rats caused a rapid increase in hepatic protein synthesis. In the present study rats force-fed a high tryptophan diet for 3 days and killed the fourth morning had increased rats of hapatic protein synthesis, cytochrome P-450 and b5 activities, in vitro nuclear RNA release (cell sap and nuclear effects) and nuclear envelope nucleoside triphosphatases activity compared to animals force-fed the control diet. We noted little or no change in hapatic total polyribosomal aggregation patterns or plasma and hepatic free amino acid levels.

Animals↗
PubMed1980

Studies on the influence of tryptophan and related compounds on hepatic polyribosomes and protein synthesis in the rat.

The effect of the administration of L-tryptophan or tryptophan-related compounds on rat liver RNA and protein metabolism was investigated. The five biochemical parameters studied were polyribosomal aggregation, protein synthesis in vitro, synthesis of cytoplasmic poly(A)-mRNA, release of labeled nuclear RNA in vitro (nuclear and cell sap effects) and nuclear envelope nucleoside triphosphatase activity. The administration of L-tryptophan to overnight fasted rats revealed a rapid stimulation in all of the five parameters. Also, some of the tryptophan-related compounds, especially 5-hydroxy-DL-tryptophan, 3-indolepyruvic acid, indole or 3-hydroxyanthranilic acid, revealed stimulation in many of the parameters. However, when rats were pretreated with puromycin to inhibit protein synthesis, only the administration of L-tryptophan was still able to stimulate significantly the hepatic polyribosomes, in vitro protein synthesis, in vitro nuclear RNA release (involving nuclei but not cell sap) and nuclear envelope nucleoside triphosphatase activity. The effects by the other tryptophan-related compounds became inhibited. The results emphasize the unique action of L-tryptophan on hepatic protein synthesis.

3-Hydroxyanthranilic Acid↗
PubMed1980

Studies dealing with hepatic RNA metabolism in rats force-fed a threonine-devoid diet.

Young rats were force-fed for 3 days a purified diet devoid of threonine and a number of aspects relating to RNA metabolism in the livers were studied. The findings in the livers of rats force-fed the threonine-devoid diet in comparison with those force-fed the complete diet were as follows: a) poly(A)-mRNA was increased in nuclei and in polyribosomes; b) DNA-dependent RNA polymerases I and II activities were increased; c) in vitro release of 14C-orotic acid labeled RNA from nuclei revealed that transport was unchanged and nucleoside triphosphatase activity of nuclear envelopes was unchanged; d) polyribosomes (total, free and membrane-bound) shifted toward heavier aggregation and in vitro 14C-leucine incorporation into protein was increased; e) RNase activities (at pH 5.4, 7.6, 9.5) were essentially unaltered; and f) in vivo 14C-choline incorporation into microsomal membranes was increased. By administering selected inhibitors of RNA and protein synthesis, such as actinomycin D, alpha-amanitin or cycloheximide, prior to killing the rats force-fed the threonine-devoid or complete diet for 3 days, it was demonstrated that the stimulatory effect on hepatic polyribosomes and protein synthesis in the experimental group was dependent upon new synthesis of poly(A)mRNA and of protein.

Animals↗
PubMed1980

Acute effect of ethanol on membranes of the endoplasmic reticulum and on protein synthesis in rat liver.

The acute effect of ethanol on the membranes of hepatic endoplasmic reticulum, on the in vitro protein-synthetic activities of hepatic free and membrane-bound polyribosomes and on the plasma proteins of rats fasted overnight was investigated. Ethanol (0.75 g/100 g body weight) was tube-fed as a 50% (v/v) solution in saline 3 hr before sacrifice. Hepatic endoplasmic reticulum membranes from control and ethanol-treated rats were compared using the following techniques: (1) lactoperoxidase-catalyzed radioiodination of proteins and sodium dodecylsulfate-polyacrylamide gel electrophoresis, and (2) measurement of 14C-choline incorporation into membranes. Hepatic microsomal membranes from ethanol-treated rats incorporated in vitro les 125I into total proteins (as well as into the 55,000 molecular weight proteins) and incorporated in vivo less 14C-choline into microsomal membranes than membranes of control rats. Ethanol administration inhibited in vivo incorporation of 14C-leucine or 14C-phenylalanine into liver protein and plasma albumin and globulin. The data also indicate that an acute dose of ethanol reduced the in vitro protein-synthetic activity of hepatic membrane-bound polyribosomes, while free polyribosomes were relatively unaffected.

Animals↗