Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.1.21 (thymidine kinase)
 7,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Estrogen and androgen receptors within the liver have been reported to modulate the hepatic regenerative response to partial hepatectomy. Moreover, cyclosporine has several untoward effects that might occur as a consequence of alterations in sex hormone activity. To evaluate these questions the following experiments were performed. Estrogen and androgen receptors in cytosol were quantitated in livers of rats treated with cyclosporine or olive oil vehicle before and after partial hepatectomy or a sham operation. Ornithine decarboxylase activity and thymidine kinase activity were assessed as indices of hepatic regeneration. Preoperative levels of estrogen receptor activity in the hepatic cytosol were significantly greater in rats treated with cyclosporine as compared to vehicle treated controls (P less than 0.01). In contrast, preoperative levels of androgen receptor activity in the cyclosporine-treated and vehicle-treated animals were similar. Following partial hepatectomy, a reduction in the activity of both sex hormone receptors in the hepatic cytosol was observed and was compatible with results described previously in normal animals. Unexpectedly the preoperative levels of ornithine decarboxylase (P less than 0.01) and thymidine kinase activity (P less than 0.01) were significantly greater in the rats treated with cyclosporine as compared to the vehicle treated controls. As expected, ornithine decarboxylase activity (at 6 hr) and thymidine kinase activity (at 24 hr) rose and peaked in response to a partial hepatectomy but were significantly greater (P less than 0.05) in the rats treated with cyclosporine as compared to the vehicle.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of cyclosporine on hepatic cytosolic estrogen and androgen receptor levels before and after partial hepatectomy. 229 96

A number of mechanisms participate in the hepatic injury that occurs during and following liver transplantation. A normal allograft regenerative response is probably essential for a successful transplant outcome. In this study, the effect of cyclosporine, a potent immunosuppressant used routinely after liver transplantation, on the regenerative response of the liver after partial hepatectomy was investigated. Male Wistar rats were pretreated for one week with either cyclosporine or the olive oil vehicle and were subjected to either a two-thirds partial hepatectomy or a sham operation. Animals were sacrificed at various times postoperatively and the remnant livers were weighed to determine the liver weight to body weight ratio, two biochemical measures of a regenerative response (cytosolic ornithine decarboxylase activity and thymidine kinase activity), and the hepatic content of estrogen and androgen receptors, as the content of these receptors has been shown to modulate, at least in part, the subsequent hepatic regenerative response. The preoperative hepatic cytosol content of ornithine decarboxylase, thymidine kinase, and estrogen receptor was significantly greater (P less than 0.05) in rats pretreated with cyclosporine than in those treated with the vehicle alone. A significant increase in ornithine decarboxylase and thymidine kinase activities occurred after partial hepatectomy in both the cyclosporine-pretreated and vehicle-pretreated animals. The absolute levels for each parameter were also greater in the cyclosporine-treated animals than in the vehicle-treated controls at 24 hr after partial hepatectomy (P less than 0.05). The pattern of change in the hepatic cytosolic content of estrogen and androgen receptors in both groups of animals was comparable with those described previously for regenerating liver.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cyclosporine augments hepatic regenerative response in rats. 230 86

Ornithine decarboxylase and thymidine kinase are enzymes that increase in activity in regenerating liver. We found that both activities and mRNA levels for these enzymes increase significantly after 70% partial hepatectomy in the rat. After sham hepatectomy (laparotomy) there were significant decreases in activity; however, mRNA content was unaltered. Similar decreases in enzyme activity, without changes in mRNA content, were found with pair-feeding, and additional decreases in activity after starvation. In contrast to previous reports of no change in ornithine decarboxylase and thymidine kinase after sham hepatectomy, the present results indicate that decreases occur. This may be mediated by the decrease in food intake after surgery. Dietary factors may be important in the physiologic regulation of these enzymes in the liver.
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PMID:Effects of partial and sham hepatectomy on ornithine decarboxylase and thymidine kinase activities and mRNA contents. 235 25

The trophic effect of one or multiple subcutaneous injections of two different doses of a cholecystokinin-like peptide (CCK-LP) on the rat pancreas was evaluated by determination of ornithine decarboxylase (ODC) activity, the concentrations of the polyamines putrescine, spermidine, and spermine, and the activities of DNA polymerase and thymidine kinase, in addition to the contents of DNA, RNA, and protein. ODC activity was increased 10- to 20-fold already 2 h after a single injection of CCK-LP. The activity thereafter decreased and approached the control level after 6 to 8 h. The concentration of putrescine also showed a marked increase after a single injection, approaching maximum at 8 h. A slight increase was found for spermidine as well. DNA polymerase and thymidine kinase increased after 2 days of treatment. The DNA content was still normal at that time. The study suggests that the trophic effect of CCK is initiated very early. It shows that ODC activity and putrescine concentrations are early and sensitive determinants of the effect of CCK on the pancreas.
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PMID:Effects of a cholecystokinin-like peptide on DNA and polyamine synthesis in the rat pancreas. 241 Sep 73

We have studied a panel of 10 genes and cDNA sequences that are expressed in a cell cycle-dependent manner in different types of cells from different species and that are inducible by different mitogens. These include five sequences (c-myc, 4F1, 2F1, 2A9, and KC-1) that are preferentially expressed in the early part of the G1 phase, three genes (ornithine decarboxylase, p53, and c-rasHa) preferentially expressed in middle or late G1, and two genes (thymidine kinase and histone H3) preferentially expressed in the S phase of the cell cycle. We have studied the expression of these genes in nonpermissive (tsAF8) and semipermissive (Swiss 3T3) cells infected with adenovirus type 2. Under the conditions of these experiments, adenovirus type 2 infection stimulates cellular DNA synthesis in both tsAF8 and 3T3 cells. However, four of the five early G1 genes (c-myc, 4F1, KC-1, and 2A9) and one of the late G1 genes (c-ras) are not induced by adenovirus infection, although they are strongly induced by serum. The other sequences (2F1, ornithine decarboxylase, p53, thymidine kinase, and histone H3) are activated by both adenovirus and serum. We conclude that the cell cycle-dependent genes activated by adenovirus 2 are a subset of the cell cycle-dependent genes activated by serum. The data suggest that the mechanisms by which serum and adenovirus induce cellular DNA synthesis are not identical.
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PMID:Adenovirus type 2 activates cell cycle-dependent genes that are a subset of those activated by serum. 242 24

Little is known about the cellular mechanisms responsible for the trophic effects of cholecystokinin (CCK) and secretin on the rat pancreas, and controversy exists with regard to the interaction between these two peptides. In the present study attempts were made to elucidate the time course of events leading to pancreatic growth and to clarify the interaction between the peptides when given as continuous, long-term intravenous infusions to rats. A cholecystokinin-like peptide (CCK-LP) and secretin were given as a continuous intravenous infusion to conscious and unrestrained animals with free access to food and water for 0.5, 1, 2, 4, 6, 8, 12, 24, 48, and 96 h. The pancreas was quickly removed and analyzed for variables indicating synthesis and accumulation of DNA, RNA, and polyamines. CCK-LP increased the activity of RNA polymerase already after 1 h, whereas an increase in the activity of ornithine decarboxylase (ODC) and the level of putrescine was seen at 4 h. Spermidine was increased after 12 h. The activities of DNA polymerase and thymidine kinase were increased at 12 and 24 h, respectively, whereas the total contents of DNA and RNA were first increased at 48 h. Secretin alone showed a marked but short-lived effect on polyamine synthesis and a weak effect on the variables indicating protein synthesis and growth. When the two peptides were given together, a large but transient potentiation of ODC activity was observed, whereas no interaction was seen on polyamines, RNA synthesis, or pancreatic growth. The present study confirms the trophic effects of CCK and secretin on the rat pancreas but fails to confirm an interaction between the two peptides on growth. Both peptides stimulate polyamine synthesis, and ODC appears to be an early and sensitive indication of their trophic effect. The initiation of RNA synthesis appears to be independent of the ODC activity.
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PMID:Short- and long-term effects of secretin and a cholecystokinin-like peptide on pancreatic growth and synthesis of RNA and polyamines. 247 84

The role played by the polyamines in mediating the pancreatic growth and secretory responses to hormonal stimulation is uncertain. The effect of an inhibitor of ornithine decarboxylase (ODC), alpha-difluoromethylornithine (DFMO), on rat pancreatic protein secretion and synthesis and on growth in response to hormonal stimulation was therefore studied. Anesthetized rats were given an intravenous injection of DFMO (50, 100, or 150 mg/kg), followed by a 7-h continuous infusion (15, 25, or 35 mg/kg/h, respectively). After a basal 1-h period an intravenous infusion of 2.5 micrograms/kg/h of the cholecystokinin-like peptide Thr28Nle31CCK25-33 (CCK-LP) was added and continued for 6 h. The control rats received CCK-LP only. The ODC activity in the pancreas was markedly reduced by DFMO, but DFMO did not affect pancreatic juice volume or protein output. In another series conscious rats were given a continuous intravenous infusion of 2.5 micrograms/kg/h of CCK-LP for 8, 24, and 48 h or 5.0 micrograms/kg/h of secretin for 8 and 48 h, with or without DFMO (100 mg/kg as an injection initially and thereafter 25 mg/kg/h). The ODC activity and putrescine concentration in the pancreas were significantly reduced by DFMO at 8 and 24 h but not at 48 h. DFMO also significantly reduced the activities of RNA polymerase, DNA polymerase, and thymidine kinase at 24 h, but not at 48 h. The present study thus indicates that polyamines play a role in the initiation of the growth response to hormonal stimulation but does not support a similar dependence for early pancreatic protein synthetic and secretory responses.
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PMID:Inhibition of polyamine synthesis by alpha-difluoromethylornithine and its effects on pancreatic secretion and growth in the rat. 247 85

Acute and long-term changes of ornithine decarboxylase and polyamines during pancreatic adaptation in response to cholecystokinin administration (1 microgram kg-1 body wt every 8 h) were studied in rats. alpha-difluoromethylornithine, an irreversible and specific inhibitor of ornithine decarboxylase, was applied simultaneously to elucidate the essential role of polyamines in pancreatic growth. In the cholecystokinin-treated animals ornithine decarboxylase activity was increased after 2 h, reached a maximum after 8 h (444.6 pmol 14CO2 h-1 mg-1 DNA, about 65-fold greater than controls, P less than 0.001) followed by a significant increase of putrescine after 6 h and spermidine after 24 h while spermine remained unchanged. The trophic parameters increased in the following time sequence: thymidine kinase (12 h), DNA polymerase (24 h), pancreatic weight (2 days), protein (2 days) and DNA (5 days). alpha-difluoromethylornithine significantly delayed the increase in ornithine decarboxylase, putrescine and spermidine as well as all trophic parameters. Increases in ornithine decarboxylase, polyamines and all trophic parameters were completely inhibited by simultaneous application of the CCK receptor antagonist L-364,718. These data indicate an important role for ornithine decarboxylase and polyamines in cholecystokinin-induced pancreatic growth in rats.
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PMID:Ornithine decarboxylase and polyamines in cholecystokinin-induced pancreatic growth in rats: effects of alpha-difluoromethylornithine and the CCK receptor antagonist L-364,718. 247 58

The dose dependence of a cholecystokinin-like peptide (CCK-LP) on the trophic response in the rat pancreas was studied. Graded doses of Thr28Nle31CCK25-33 (0.02, 0.1, 0.5, 2.5, and 12.5 micrograms/kg/h) or saline were given as a continuous intravenous infusion to conscious and fed rats for 8 and 48 h. Secretin (5.0 micrograms/h) was given alone or combined with the three highest doses of CCK-LP for 48 h. CCK-LP showed a dose-dependent stimulating effect on pancreatic growth and synthesis of RNA and polyamines. The threshold dose ranged from 0.02 to 0.5 micrograms/kg/h and was lowest for stimulation of ornithine decarboxylase (ODC). The maximal effects on protein, RNA, and DNA contents were achieved with 2.5 micrograms/kg/h. These same variables markedly decreased with 12.5 micrograms/kg/h, whereas marked further increases were found for the activities of RNA polymerase, DNA polymerase, and thymidine kinase. This same dose of CCK-LP caused after 8 h of treatment a marked and transient increase in pancreatic weight, activity of ODC, and concentration of putrescine. When secretin was added to 0.5 and 2.5 micrograms/kg/h of CCK-LP, no additional effect (except for ODC) was found. When secretin was added to the highest dose of CCK-LP, the decreased contents of protein and RNA were significantly increased, and the markedly increased activities of RNA- and DNA-synthesizing enzymes were significantly decreased. The present study shows a clear dose-response relationship for the trophic effect of CCK-LP on the rat pancreas and indicates that the growth effect of a supramaximal dose includes components of regeneration secondary to damage.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effects of graded doses of a cholecystokinin-like peptide with and without secretin on pancreatic growth and synthesis of RNA and polyamines in rats. 248 Jun 34

This study was designed to investigate changes of ornithine decarboxylase and polyamines during pancreatic adaptation in response to feeding of the synthetic protease inhibitor camostate. alpha-Difluoromethylornithine, an irreversible and specific inhibitor of ornithine decarboxylase, was applied simultaneously to elucidate the essential role of polyamines in pancreatic growth. Cholecystokinin (CCK) plasma levels in camostate-fed rats increased from basal values of 3-4 pmol/l to a maximal level of 27.4 pmol/l after 2h; they then decreased up to 12 h but remained elevated above controls throughout the 30-day experiments. In the camostate group pancreatic ornithine decarboxylase activity was elevated after 2 h, reaching a maximum after 6 h (1,858.5 pmol 14CO2/h/mg DNA, about 200-fold above controls) followed by a significant increase in putrescine after 4 h and spermidine after 24 h while spermine remained unchanged. The trophic parameters increased in the following time sequence: thymidine kinase (12 h), DNA polymerase (12 h), protein (24 h), pancreatic weight (24 h) and DNA (5 days). alpha-Difluoromethylornithine significantly delayed and reduced the camostate-induced increase in ornithine decarboxylase activity and polyamine concentrations as well as the trophic parameters. Application of the CCK receptor antagonist L-364,718 resulted in complete inhibition of the increases in ornithine decarboxylase, polyamines and all trophic parameters. These data indicate an important role for ornithine decarboxylase and polyamines in camostate-induced pancreatic growth and hormonal mediated pancreatic adaptation in rats.
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PMID:Role of ornithine decarboxylase and polyamines in camostate (Foy-305)-induced pancreatic growth in rats. 250 68


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