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)

After massive liver injury with acetaminophen, subcoma doses of hepatic failure toxins (NH+4, dimethyl disulfide [----methanethiol], octanoic acid) depressed liver thymidine kinase (TK) activity by 78%, 85%, and 90%, respectively, and ornithine decarboxylase (ODC) activity by 40%, 83%, and 78%, respectively. Twenty-four hours after the last dose of the toxins the depressant effects were still evident. The doses of dimethyl disulfide and octanoic acid required for these depressant effects on TK activity were less than half those required for similar effects previously reported after two-lobe hepatectomy of normal rat liver. The dose of NH+4 required was not reduced. None of the toxins depressed ODC activity after the hepatectomy, in contrast to their depressant effects after acetaminophen. Thus doses of the hepatic failure toxins that were about one fourth to one half those needed to induce coma in normal rats inhibited activity of regenerative enzymes after acute massive liver injury with acetaminophen. The effects were persistent for at least 24 hours. These observations may have relevance to the lack of regeneration observed commonly after fulminant hepatic failure in humans.
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PMID:Effect of hepatic failure toxins on liver thymidine kinase activity and ornithine decarboxylase activity after massive necrosis with acetaminophen in the rat. 405 69

The role of polyamine in the proliferation of cultured mouse L cells was investigated using DL-alpha-hydrazino-delta-aminovaleric acid (DL-HAVA), a potent and competitive inhibitor of ornithine decarboxylase [EC 4.1.1.17]. When confluent mouse L cells were reseeded, the intracellular concentration of polyamines increased sharply, and the maximal levels of putrescine, spermidine, and spermine were 3.3, 2.2, and 1.8 times their initial values, respectively, one or two days after inoculation. DL-HAVA produced prompt depletion of the intracellular putrescine and spermidine contents and a further increase of the spermine level to 30-90% more than that of the control throughout the experiment. The total level of the three polyamines was reduced to a great extent in DL-HAVA-treated cells. Concomitant with the disappearance of the two polyamines, cell proliferation, measured as the total cell number and DNA accumulation, was greatly suppressed by the inhibitor. Addition of exogenous putrescine or spermidine with or after DL-HAVA restored the inhibited cell growth in a dose-dependent manner. Putrescine administered to inhibitor-treated cultures was rapidly incorporated into the cells and effectively converted to spermidine. Addition of spermidine to the culture medium also normalized the intracellular spermidine content, but the putrescine level remained unchanged. Neither cadaverine nor 1,3-diaminopropane, structural analogs of putrescine, overcame the inhibition under the same conditions. Thymidine kinase [EC 2.7.1.21] activity and the pools of triphosphates of thymidine and deoxyadenosine were appreciably reduced in DL-HAVA-treated cells, whereas DNA polymerase [EC 2.7.7.7] activity was not changed significantly. These findings suggest that spermidine might play essential roles in the metabolism of deoxyribonucleoside triphosphates and growth of mouse L cells in culture.
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PMID:Inhibition of polyamine synthesis and proliferation in mouse L cells by DL-alpha-hydrazino-delta-aminovaleric acid, an inhibitor of ornithine decarboxylase. 661 23

Lymphocyte mitogenesis is generally assessed by measuring the incorporation of [(3)H]thymidine into DNA. By this criterion, small lymphocytes, which are activated by relatively low doses of concanavalin A, are either unresponsive to or inhibited by higher concentrations. Because lymphocytes begin to synthesize DNA about 24 hr after addition of mitogen, the response is far removed temporally from the initial stimulus. We have chosen to use the induction of S-adenosylmethionine decarboxylase (S-adenosyl-L-methionine carboxy-lyase, EC 4.1.1.50) to assess early activation events in bovine lymphocytes. Adenosylmethionine decarboxylase induction is bimodal, with an initial phase beginning 3 hr after addition of concanavalin A and a second wave coinciding with the onset of DNA synthesis. The initial accumulation of the decarboxylase (0-9 hr) in cultures treated with "nonmitogenic" levels of concanavalin A (108 mug/ml) was similar to that observed in cultures stimulated with optimally mitogenic doses (18 mug/ml). The early induction of ornithine decarboxylase (L-ornithine carboxy-lyase, EC 4.1.1.17) was also similar under these two culture conditions. However, the second phase of adenosylmethionine decarboxylase accumulation, the induction of thymidine kinase (ATP: thymidine 5'-phosphotransferase, EC 2.7.1.21), and DNA replication were blocked at the higher concentrations of concanavalin A. The inhibition of late events by high doses of concanavalin A was reversible. Cells treated with alpha-methyl-D-mannopyranoside 25 hr after addition of a high dose of lectin responded with a second period of adenosylmethionine decarboxylase accumulation, induction of thymidine kinase, and progression through S phase. These results suggest that initial lymphocyte activation occurs normally at high doses of concanavalin A, but that the cells are reversibly blocked prior to induction of "late" enzymes and progression through S phase.
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PMID:Activation of early enzyme production in small lymphocytes in response to high, nonmitogenic concentrations of concanavalin A. 693 33

Biochemical events were investigated in the G1 to S phase progression induced in quiescent rodent cells by human adenovirus type 5 (Ad5) and by serum. Thymidine kinase activity increased after infection of cells with Ad5 or addition of 10% serum. These stimulations were additive. An early viral gene was responsible for induction by Ad5, but the early mutants ts36, ts37, and ts125 induced thymidine kinase at the permissive and nonpermissive temperatures. Several differences were found between cells stimulated by serum compared with Ad5. Induction of thymidine kinase was delayed in Ad5-infected cells, insensitive to 0.01 microgram/ml actinomycin D and relatively resistant to reduced Ca2+ compared with induction by serum. Ornithine decarboxylase was induced by serum, but not by Ad5, alpha-Methylornithine had little effect on the induction of thymidine kinase by Ad5, but reduced the induction of thymidine kinase by serum, suggesting that Ad5-induced entry into S phase is uncoupled from polyamine biosynthesis. Methylglyoxal bis(guanylhydrazone), however, prevented the induction of thymidine kinase by both serum and Ad5. Adenovirus infection appears to induce cellular DNA synthesis and thymidine kinase in G1-arrested cells by a mechanism different from serum, and bypasses events in the normal G1 to S phase progression.
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PMID:A biochemical investigation of the adenovirus-induced G1 to S phase progression: thymidine kinase, ornithine decarboxylase, and inhibitors of polyamine biosynthesis. 706 69

Adenovirus type 5 induces cellular DNA synthesis and thymidine kinase in quiescent rat cells but does not induce ornithine decarboxylase. We now show that unlike serum, adenovirus type 5 fails to induce S-adenosylmethionine decarboxylase or polyamine accumulation. The inhibition by methylglyoxal bis(guanylhydrazone) of the induction of thymidine kinase by adenovirus type 5 is probably unrelated to its effects on polyamine biosynthesis. Thus, induction of cellular thymidine kinase and DNA replication by adenovirus type 5 is uncoupled from polyamine accumulation.
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PMID:Adenovirus type 5 induces progression of quiescent rat cells into S phase without polyamine accumulation. 717 12

A temperature-sensitive (ts) cell cycle mutant of Chinese hamster fibroblasts with a block in G1 was investigated. Attention was on the expression of the activity of three enzymes: ornithine decarboxylase (ODC) S-adenosylmethionine decarboxylase (SAMDC), and thymidine kinase (TK). ODC and SAMDC activities are normally induced in the middle of, or late in, the G1 phase, while TK activity starts to appear at the G1/S boundary. In the ts mutant released from serum starvation at the nonpermissive temperature (40.8 degrees C), we find no effect on the expression of SAMDC activity, a significantly reduced level of ODC activity compared to the control at the permissive temperature (34 degrees C), and no induction of TK activity. Results presented here and in a previous publication (Landy-Otsuka and Scheffler, '78) suggest that the decrease in ODC activity is due to an effect of the nonpermissive temperature on a post-transcriptional step, possibly a very rapid inactivation of the enzyme. The absence of TK activity, on the other hand, appears to be due to a block in transcription at the nonpermissive temperature.
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PMID:Enzyme induction in a temperature-sensitive cell cycle mutant of Chinese hamster fibroblasts. 746 27

Na(+)-K(+)-adenosinetriphosphatase (ATPase) plays a key role in the absorption of electrolytes, water, and nutrients from the small intestine. The expression of Na(+)-K(+)-ATPase was examined in isolated enterocytes during the course of the ileal inflammatory response elicited by intraluminal administration of 2,4,6-trinitrobenzenesulfonic acid. The ileal inflammatory response was characterized by a marked cellular infiltrate, villous atrophy, and crypt hyperplasia along with fibrosis and smooth muscle hypertrophy. Peak levels of myeloperoxidase were observed at day 7, and ileal mucosal injury was paralleled by increases in ileal mucosal permeability. Ileal enterocytes were harvested from days 3 to 30 after the induction of ileitis. Decreases in Na(+)-K(+)-ATPase functional activity were observed from days 3 to 21 and were accompanied by corresponding decreases in Na(+)-K(+)-ATPase pump abundance, alpha 1- and beta 1-protein expression, and mRNA abundance, whereas Na(+)-K(+)-ATPase turnover, Michaelis-Menten constant values, and inhibition constant values for Na+ and ouabain, respectively, were unaltered. Alterations in transcriptional and posttranscriptional events may determine the changes in Na(+)-K(+)-ATPase activity in this particular model. Additionally observed increases in thymidine kinase and ornithine decarboxylase activities appear to signify alterations in the state of differentiation of the ileal epithelium and may determine the phenotypic expression of enterocyte transporters and permeability in the setting of inflammation.
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PMID:Na(+)-K(+)-ATPase alpha 1- and beta 1-mRNA and protein levels in rat small intestine in experimental ileitis. 749 57

It has been shown previously that liver regeneration after partial hepatectomy in rats is delayed if the liver is subjected to either concurrent ischaemia, flushing with cold solution, or grafting. We have shown recently that treatment with CsA preoperatively overcomes the suppressive effect of flushing and returns the regenerative response to a normal time scale. The present study was designed to investigate whether administration of FK506 would also return the observed delayed regenerative response to normal. Long-Evans rats weighing 250-350 g were subjected to standard 68% partial hepatectomy. Group 1 had no further treatment; in group 2, the liver remnant was flushed with 10 ml cold (4 degrees C) Ringers lactate solution, and in group 3, FK506 (1 mg/kg/day) was administered by intramuscular injection for 3 days before the partial hepatectomy and flushing as in group 2; a final dose was given after completion of the procedures. Animals were killed in sets of 6 per group at 4, 24, 48, 72, and 96 hr after surgery and blood samples were taken for measurement of plasma aspartate amino-transferase. Liver biopsies were analyzed for measurement of thymidine kinase and ornithine decarboxylase activity and for counting of mitotic figures. While the highest recorded thymidine kinase activity occurred in group 1 at 24 hr, this was delayed to 48 hr in both group 2 and 3 and counts remained high up to 96 hr in group 3. Mitotic indices were only significantly elevated (compared with group 1 at 96 hr), while ornithine decarboxylase activity did not correlate with these changes being significantly lower than in groups 2 and 3 at 4 hr and in group 3 also at 24 hr. Plasma aspartate aminotransferase was also significantly higher in group 3. It is concluded that the administration of FK506 preoperatively to rats subjected to partial hepatectomy and flushing did not restore the delayed regenerative response to normal but enhanced the response (as measured by thymidine kinase but not by mitotic indices) which commenced at 48 hr and was still present at 96 hr.
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PMID:The effect of administration of FK506 on delayed regeneration in flushed partially hepatectomized livers. 751 Dec 55

Mitogenic stimulation of quiescent cells not only triggers the cell division cycle but also induces an increase in cell volume, associated with an activation of cellular metabolism. It is therefore likely that genes encoding enzymes and other proteins involved in energy metabolism and biosynthetic pathways represent a major class of mitogen-induced genes. In the present study, we investigated in the non-established human fibroblast line WI-38 the induction by mitogens of 17 genes whose products play a role in different metabolic processes. We show that these genes fall into 4 different categories, i.e. non-induced genes, immediate early (IE) primary genes, delayed early (DE) secondary genes and late genes reaching peak levels in S-phase. In addition, we have analysed the regulation of these genes during normal cell cycle progression, using HL-60 cells separated by counterflow elutriation. A clear cell cycle regulation was seen with those genes that are induced in S-phase, i.e. thymidine kinase, thymidylate synthase and dihydrofolate reductase. In addition, two DE genes showed a cell cycle dependent expression. Ornithine decarboxylase mRNA increased around mid-G1, reaching maximum levels in S/G2, while hexokinase mRNA expression was highest in early G1. In contrast, the expression of other DE and IE genes did not fluctuate during the cell cycle, a result that was confirmed with elutriated WI-38 and serum-stimulated HL-60 cells. These observations suggest that G0-->S and G1-->S transition are distinct processes, exhibiting characteristic programmes of gene regulation, and merging around S-phase entry.
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PMID:Differential induction of 'metabolic genes' after mitogen stimulation and during normal cell cycle progression. 751 13

Partial hepatectomy (60%) led to the biphasic increase (first one at 4 h and second one at 48 h) of ornithine decarboxylase activity in the remnant rat liver. Daily administration of 3,5,3'-L-triiodothyronine (T3) (10 micrograms/100 g) to rats for 7 days before partial hepatectomy had little effect on the enzyme activity. At five days, ornithine decarboxylase activity declined to control level (sham operated controls) and its activity was significantly enhanced by T3. Ornithine decarboxylase gene expression in the rat liver (examined by Northern blot analysis using poly A+ mRNA) started to increase 4 h after partial hepatectomy, remained elevated for 48 h and decreased after 5 days. Its activity was not altered by T3 treatment. The activity of thymidine kinase increased progressively after partial hepatectomy, but its peak value was delayed by T3 administration. Plasma prolactin levels increased within 5-15 min after liver resection, then declined to control values and increased 24 h after the surgery. The data demonstrate that the changes in ornithine decarboxylase activity in the rat liver after partial hepatectomy might result from the direct effect of prolactin on the activity of enzyme rather than from its induction by hormone. Triiodothyronine administration altered both ornithine decarboxylase and thymidine kinase activities suggesting that T3 appears to regulate ornithine decarboxylase activity at post-translational level.
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PMID:Effect of 3,5,3'-L-triiodothyronine on hepatic ornithine decarboxylase and thymidine kinase activity in rat after partial hepatectomy. 771 Dec 95


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