Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.1.21 (thymidine kinase)
7,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The length of the prereplicative period after stimulation of quiescent WI-38 cells is prolonged in proportion to the length of time the cells are incubated prior to serum addition. Previous results from this laboratory have shown that this prolongation does not result from a delay in the induction of events which occur during the G0/G1 transition (i.e. c-fos or c-myc expression) (Owen, T., Cosenza, S., Soprano, D. R., and Soprano, K. J. (1987) J. Biol. Chem. 262 15111-15117). It was the goal of the present studies to examine the expression of other growth-associated genes known to be induced and maximally accumulate later in G1 to identify genes whose expression is coupled to entry into S rather than mitogenic stimulation. In order to do this, the temporal pattern of expression of a variety of growth-associated genes (thymidine kinase, p53, 2A9/calcyclin, ornithine decarboxylase, 4F1/vimentin, and c-Ha-ras) was studied in WI-38 cells stimulated either 12 days or 26 days after plating. We report that the time of induction and maximum accumulation of each of these transcripts, with the exception of c-Ha-ras, was delayed in the 26-day cell group for 10 h, a period of time approximately equal to the length of delay in entry of these cells into S. Thus the expression of these particular genes would appear to be closely coupled in time and sequence to the entry of cells into S. These results suggest that the prolongation of the prereplicative period in WI-38 cells is located in early G1, following the events leading to c-fos and c-myc induction but prior to the induction and maximum accumulation later in G1 of other growth-associated genes such as ornithine decarboxylase and 4F1/vimentin. In addition, these results provide molecular evidence for a definitive programmed order of gene expression during the progression of cells out of G0 through G1 to S.
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PMID:Evidence that the time of entry into S is determined by events occurring in early G1. 313 30

Previous studies have shown that male rat liver undergoes demasculinization during hepatic regeneration after partial hepatectomy. In the present study the effect of the antiandrogen flutamide on liver regeneration was assessed. Adult male Wistar rats were treated with flutamide (2 mg/rat/day or 5 mg/rat/day subcutaneously) or vehicle for 3 days prior to and daily after partial hepatectomy. Rates of DNA and polyamine synthesis were assessed by measuring thymidine kinase and ornithine decarboxylase activities, respectively. The rate of liver growth after partial hepatectomy in the three groups was similar at all time points examined. The increases in thymidine kinase activity and ornithine decarboxylase activity after partial hepatectomy were comparable throughout the study. Thus, administration of flutamide did not influence the regenerative response after partial hepatectomy.
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PMID:Liver regeneration in rats treated with the antiandrogen flutamide. 315 86

To evaluate the effect of portal hypertension and diminished portal venous blood flow to the liver on hepatic regeneration, male rats were subjected to partial portal vein ligation and subsequently to a two-thirds partial hepatectomy. The levels of ornithine decarboxylase activity at 6 h after partial hepatectomy were greater (p less than 0.001) in the rats with prior partial portal vein ligation than in those without portal hypertension. The rats with prior partial portal vein ligation also had greater (p less than 0.005) levels of thymidine kinase activity at 48 h after partial hepatectomy than did those without portal hypertension. Hepatic sex hormone receptor activity was not affected by prior partial portal vein ligation either before or after partial hepatectomy. The reductions in both estrogen and androgen receptor activity observed in the hepatic cytosol after partial hepatectomy were similar to those observed in control animals. These data indicate that animals with portal hypertension having a diminished hepatic portal blood flow have a normal capacity to regenerate hepatic mass following a hepatic resection.
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PMID:Effect of partial portal vein ligation on hepatic regeneration. 315 99

Transforming growth factor beta (TGF-beta) was found to inhibit (IC50 = 0.1 ng/ml) alpha-thrombin or FGF-induced mitogenicity in G0-arrested Chinese hamster lung fibroblasts. Growth factor-stimulated cells became rapidly insensitive to TGF-beta addition during their progression through G0/G1 suggesting that an early step of the mitogenic response was the target of TGF-beta action. Surprisingly, none of the well characterized early mitogenic events commonly triggered by growth factors was found to be affected by TGF-beta addition. These responses included: phosphoinositide breakdown, activation of protein kinase C as determined by EGF receptor down-modulation, subsequent rises in pHi, c-fos, and c-myc mRNA levels, ribosomal protein S6 phosphorylation, the increase in RNA and protein synthesis, induction of ornithine decarboxylase. Only the induction of thymidine kinase, a marker of entry in the S phase, was found to be repressed by TGF-beta, with maximal inhibition when TGF-beta was added early in G1. These results indicate that the inhibitory action of TGF-beta does not affect the growth factors signalling pathways but touches an early event different from those so far analyzed.
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PMID:TGF-beta inhibits growth factor-induced DNA synthesis in hamster fibroblasts without affecting the early mitogenic events. 316 35

Massive liver injury with 1000 mg/kg D-galactosamine was followed by a broad peak of thymidine kinase (TK) activity over 62 to 120 hours. The highest mean value was a 29-fold increase in activity. Three peaks of ornithine decarboxylase (ODC) activity were observed over the same time span. The first peak occurred at 45 hours, showing a sevenfold to eightfold increase in activity. Histologic evidence of necrosis peaked at 12 to 24 hours and was prominent over 54 hours. Periportal inflammation in response to the cellular injury was prominent from 12 to 96 hours and peaked at 45 to 62 hours. The curve of mitoses peaked at the same time as that of TK activity but was only 68% as extensive. The first peak of ODC activity occurred before there was any significant presence of mitoses or of TK activity. A smaller dose of 400 mg/kg resulted in a narrow peak of TK activity at 62 hours that was a 37-fold increase in activity. The total TK response was 43% of that seen after the larger dose, about in proportion to the dose given. The first ODC peak, representing the earliest evidence of regeneration, was earlier and more prominent after the 400 mg/kg dose. On the basis of areas under the curves, the amounts of necrosis and of periportal inflammation after 400 mg/kg were 36% of those seen after 1000 mg/kg. Corresponding figures for other response curves were 29% for mitoses, 33% for serum SGPT, and 71% for total ODC activity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hepatic regenerative enzyme activity after diffuse injury with galactosamine: relationship to histologic alterations. 318 90

Prolactin, administered exogenously, has been shown to be trophic to the liver, causing increases in the liver weight-to-body weight ratio. In ornithine decarboxylase activity, and in thymidine kinase activity. To investigate the effect of endogenous hyperprolactinemia on hepatic regeneration, pituitary isografts were placed beneath the renal capsule in rats 2 weeks before the rats underwent a two-thirds partial hepatectomy. Prolactin levels 2 weeks after the transplant were greater in the animals with the pituitary isografts compared with levels in controls. The increase in the liver weight-to-body weight ratio after hepatectomy was similar in the rats with pituitary transplant and the controls. However, chronic hyperprolactinemia was associated with increased basal levels of ornithine decarboxylase activity and thymidine kinase activity. Both ornithine decarboxylase activity and thymidine kinase activity increased after partial hepatectomy, and the magnitude of the changes was similar for both groups of animals. The levels of estrogen receptor activity before the partial hepatectomy and the reduction in receptor activity that follows partial hepatectomy were similar in the two groups of animals. Moreover, the levels of androgen receptor activity within the liver before partial hepatectomy and the increase in receptor activity after hepatectomy were similar in the two groups of animals. Thus, chronic sustained hyperprolactinemia has no beneficial effect on the hepatic regenerative response, despite induction of both basal ornithine decarboxylase and thymidine kinase activities.
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PMID:Does hyperprolactinemia affect hepatic regeneration independent of sex steroids? 318 97

This study was designed to investigate the role of ornithine decarboxylase (ODC) and polyamines in pancreatic adaptation. Cholecystokinin (CCK) is well-known to be a potent trophic stimulus on the pancreas. On the other hand, the oral application of the synthetic trypsin inhibitor camostate results in an extensive release of endogenous CCK in rats. alpha-difluoromethylornithine (DFMO), an irreversible and specific inhibitor of ODC, was applied simultaneously to elucidate the essential role of polyamines in pancreatic growth. Camostate feeding (200 mg/kg b.wt. orally twice a day) resulted in a rapid elevation of ODC activity already after 2 hours, reaching a maximum after 6 hours (about 200fold above controls) followed by a significant increase in putrescine after 4 hours and spermidine after 24 hours while spermine remained unchanged. The trophic parameters increased as expected in following time-course: thymidine kinase (12 hours), DNA polymerase (12 hours), protein (24 hours), pancreatic weight (24 hours) and DNA (5 days). DFMO (2% in drinking water + 3 x 300 mg/kg b.wt. i.p. during daytime) was not able to prevent but significantly delayed and reduced the camostate-induced increase in ODC and polyamines as well as the trophic parameters. These data indicate an essential role for ODC and polyamines in camostate-induced pancreatic growth and hormonal mediated pancreatic adaptation.
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PMID:Ornithine decarboxylase and polyamine biosynthesis in pancreatic adaptation. 325 34

A low concentration (0.6 micrograms/ml) of cytochalasin D inhibits the initiation of DNA synthesis after serum stimulation of growth-arrested GC-7 cells. Since actin-containing structures are suggested to be involved in the transfer of the growth signal to nuclei and in the synthesis and transport of nascent RNA, the effect of cytochalasin D on the expression of cell-cycle-regulated genes after serum stimulation was studied by Northern blot analysis. Cytoplasmic accumulation of such mRNAs as or c-fos, c-myc, beta-actin an ornithine decarboxylase occurred in serum-stimulated cells regardless of the presence of cytochalasin D, whereas that of thymidine kinase and histone H3 was blocked by the drug.
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PMID:Expression of cell-cycle-dependent genes in serum stimulated cells whose entry into S phase is blocked by cytochalasin D. 329 58

Hepatic regenerative enzyme (thymidine kinase and ornithine decarboxylase) activities were significantly depressed by subcoma doses of the hepatic failure toxins (NH4+, octanoic acid, and dimethyl disulfide) after selective injury with allyl alcohol. The inhibitory effect of NH4+ was greater than that of dimethyl disulfide, even though the neurologic effects of dimethyl disulfide were approximately comparable with those of the NH4+. There appeared to be a delay in the full expression of the depressive effects of octanoic acid and dimethyl disulfide. The resistance to these two toxins, particularly dimethyl disulfide, may reflect the resistance to injury of the oxidative processes prominent in periportal hepatocyte mitochondria. In comparison with pericentral injury or two-lobe hepatectomy, periportal injury seemed equally susceptible to regenerative enzyme inhibition by NH4+ but less susceptible to the effect of octanoic acid and dimethyl disulfide.
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PMID:Hepatic failure toxins depress liver regenerative enzymes after periportal injury with allyl alcohol in the rat. 337 15

Because biochemical "feminization" of the liver in males is observed with hepatic regeneration and because the hepatic regenerative response in females is greater than that in males, the possibility that antiandrogens might potentiate liver regeneration was investigated. Before 70% hepatectomy, adult male Wistar rats were treated with cimetidine, an antiandrogenic H2 antagonist, at doses up to 10 times greater than those used clinically. Control animals received either the saline vehicle or ranitidine, an H2 antagonist without antiandrogenic properties. Treatment with cimetidine reduced the hepatic cytosolic androgen receptor content compared with ranitidine treatment. Hepatectomy caused a further reduction in androgen receptor activity in all groups. Hepatic cytosolic estrogen receptor activity was comparable in all groups throughout the study. Moreover, the rate of liver growth and the levels of ornithine decarboxylase and thymidine kinase activity induced as part of the regenerative response were similar in all groups. Thus, cimetidine, despite its ability to bind to androgen receptors, and ranitidine, an H2 receptor antagonist without antiandrogen action, do not modulate the hepatic regenerative response to a 70% partial hepatectomy.
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PMID:Effect of an antiandrogenic H2 receptor antagonist on hepatic regeneration in rats. 339 26


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