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)

BOT-2 cells (human breast tumor origin) have an impaired ability to utilize exogenous thymidine. Previous studies revealed this deficiency to be the permeation event rather than phosphorylation, since the cells have active thymidine kinase. Chromosome-mediated gene transfer was used to transfer genetic information in the form of metaphase chromosomes, from HeLa-65 cells to the BOT-2 cells, correcting the permease deficiency. Poly-L-ornithine or lipochromes were used for facilitation of chromosome uptake. After selection on HAT medium, transferant clones were isolated at a frequency of 4 x 10(-5) and 1 x 10(-5), respectively. Transferants MGP-1 and MGL-1 are stable after 18 months and have been characterized on the bases of purine and pyrimidine nucleoside uptake, relative thymidine kinase activities, alkaline phosphatase activities, and hydrocortisone-induced alkaline phosphatase activity. MGP-1 demonstrates positive thymidine uptake and incorporates radiolabeled thymidine into DNA. MGL-1 remains thymidine transport-deficient and surveys on HAT by increasing endogenous dihydrofolate reductase activity. Alkaline phosphatase activity in MGL-1 is similar to HeLa-65, 2% of that in BOT-2, and in addition, is inducible 25-30-fold by 3 micro M hydrocortisone. We have separated, genetically, a thymidine permease function from phosphorylation in cells of human origin and have transferred genetic information for the regulation of alkaline phosphatase.
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PMID:Alteration of human breast tumor cell membrane functions by chromosome-mediated gene transfer. 23 36

Current evidence suggests that intestinal crypt and villus cells have different functions in electrolyte transport. To study the regulation of transporters, we isolated and separated these two cell types. This was accomplished by sequential collection of enterocytes from rabbit ileal loops incubated with buffered solutions of calcium chelators. Alkaline phosphatase and thymidine kinase activity, sodium-glucose cotransport, and morphological criteria were used to determine cell separation. Cell viability was evaluated with trypan blue exclusion, leucine incorporation into protein, and morphological features. The role of Na(+)-H+ and Cl(-)-HCO3- exchange in the regulation of intracellular pH was analyzed using an intracellular pH sensitive dye, BCECF. Removal of external Na+ or the addition of amiloride resulted in acidification of both crypt and villus cells. Removal of Cl- or the addition of DIDS resulted in alkalinization of both cell types. The cells could be acidified with NH4Cl, and recovery from this acid load was dependent on Na+ and inhibited by amiloride. Similarly, the cells could be alkalinized with propionate and recovery was Cl- dependent and DIDS sensitive. These data are consistent with the presence of Na(+)-H+ and Cl(-)-HCO3- exchange in both crypt and villus cells. Both exchanges appear to be involved in the regulation of basal pH as well as in recovery from alterations in intracellular pH. Having demonstrated the presence of Na(+)-H+ and Cl(-)-HCO3- exchange activity in both crypt and villus cells, we can now use these cells to determine the regulation of these exchangers by intracellular second messengers.
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PMID:pH regulation in ileum: Na(+)-H+ and Cl(-)-HCO3- exchange in isolated crypt and villus cells. 184 9

The potential therapeutic effects of differentiating agents on leukemic and solid tumor cells are being evaluated worldwide. These effects can be followed by morphologic as well as biochemical parameters. The enzymatic profile of four enzymes and the level of carcinoembryonic antigen were studied in 24 human colorectal carcinoma specimens and their adjacent uninvolved mucosa. The enzymes studied were thymidine kinase and 6-phosphogluconate dehydrogenase as markers of proliferation, and alkaline phosphatase and gamma-glutamyl transpeptidase as markers of differentiation. A consistent finding was a marked increase in the activities of thymidine kinase and 6-phosphogluconate dehydrogenase in the tumor cells as compared with the adjacent normal mucosa. The activity of gamma-glutamyl transpeptidase was not significantly different between tumor and uninvolved colon tissue. Alkaline phosphatase activity was markedly reduced in the tumor specimens. A relationship between the degree of differentiation and the degree of penetration and CEA expression was demonstrated in the tumor specimens as well as in their surrounding uninvolved mucosa.
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PMID:Biochemical tissue markers of human colorectal carcinoma. 289 33

The vitamin D-dependent calcium-binding protein (CaBP) was studied in relation to the age of the cell, in isolated epithelial cell populations removed from rat duodenum. Alkaline phosphatase and thymidine kinase activities were used as markers to characterize differentiated villus cells and undifferentiated (mitotically active) crypt cells, respectively. CaBP distribution along the length of the villus, as established by radioimmunoassay, appears as a gradient increasing from the crypt to the tip of the villus. CaBP concentration in cells is shown to be (i) negatively correlated with the thymidine kinase activity of cells, and (ii) positively correlated with the alkaline phosphatase activity of cells. This indicates that CaBP is absent in crypt cells and appears in differentiated cells with the development of the brush border. Thus CaBP, like alkaline phosphatase, can be considered as an indicator of enterocyte maturation. These data were also confirmed by studying the cellular localization of the protein. In addition both indirect immunofluorescence and immunoperoxidase staining methods reveal that antibody against CaBP decorates the terminal web, but not the microvilli of the brush border of mature absorptive cells. The results suggest that CaBP may act as a modulator of some Ca2+-mediated biochemical processes at the level of the enterocyte brush border.
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PMID:Intestinal calcium-binding protein. A protein indicator of enterocyte maturation associated with the terminal web. 743 96

Acetaminophen (APAP) is a widely-used analgesic and a known hepatotoxic agent. Vascular endothelial growth factor (VEGF) is a growth factor with multiple functional roles. VEGF plays an important role in angiogenesis and hepatic regeneration. The aim of this study was to determine the expression of VEGF isoforms and its receptors throughout liver regeneration after the administration of a toxic dose of APAP in rats. Ten groups of adult male rats received a dose of 3.5 g/kg b.w. of APAP per os. The rats were killed post administration at 0-288 h. Blood and liver tissue were extracted. Determination of serum transaminases and alkaline phosphatase activities was performed. Liver injury and regeneration were assessed with hematoxylin-eosin specimens, morphometric analysis, hepatic thymidine kinase assay and Ki-67 expression. Reverse transcription-polymerase chain reaction and immunohistochemical methods were used for assessment of VEGF isoforms and receptors differential expression. High activities of aspartate aminotransferase were observed at 24 and 36 h with another peak of activity at 192 h post administration. Alanine aminotransferase was highest at 36 h. Alkaline phosphatase was increased post 24 h being higher at 72,192 and 240 h. Centrilobular necrosis was observed at 48-72 h and thorough restoration of the liver microarchitecture was observed at 288 h. Liver regeneration lasted from 24-192 h according to the results from thymidine kinase activity and Ki-67 expression. VEGF and VEGF receptor-2 m-RNA levels presented with a three-peak pattern of expression at 12-24, 72-96 and 192-240 h post administration. Significant difference was noted between periportal and centrilobular immunohistochemical expression. VEGF proves to play a critical role during APAP-induced liver regeneration as it presents with three points of higher expression. The first two time points are associated with the initial inflammatory reaction to the noxious stimulus and the hepatocyte regenerative process where as the third one is indicative of the potential involvement of VEGF in processes of remodeling.
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PMID:VEGF isoforms and receptors expression throughout acute acetaminophen-induced liver injury and regeneration. 1743 90

The incorporation of(3)H-thymidine into DNA in the brains of the 17-day and 20-day old rat fetuses was significantly reduced by maternal zinc restriction during pregnancy. The activity of the enzyme thymidine kinase (EC 2.7.1.21) was similarly reduced in the zine-deprived fetal brains on days 14 and 20 of gestation, but not on day 17. Fetal brain alkaline phosphatase (EC 3.1.3.1) was significantly depressed by maternal zinc deprivation on days 17 and 20 of pregnancy.The data suggest an association between thymidine kinase and the reduced incorporation of(3)H-thymidine into DNA in the brains of 20-day old fetuses but not in animals on day 17. Alkaline phosphatase was however depressed at this stage.The suggestion is made that because of the complexity of brain development, future biochemical studies in this area should concern specific structures in the brain at particular critical stages during neurogenesis.
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PMID:Incorporation of(3)H-thymidine into DNA and the activity of alkaline phosphatase in zinc-deficient fetal rat brains. 2427 50