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)

We determined DNA synthesis, cell turnover and cell migration in 72-h fasted and control neonatal rabbits because acute neonatal malnutrition causes specific regional alterations in brush border structure and function. Decreased cell turnover and/or migration might partly explain these observations. We injected fed and fasted neonatal rabbits with [3H]thymidine. At 1 and 72 h after injection we assessed cell proliferation and migration. Villus height was less in proximal small bowel from fasted rabbits (PF) than in fed controls (PC). Villus height was lower in proximal than in distal small bowel from fasted rabbits (DF). DNA synthesis, as measured by incorporation of [3H]thymidine into DNA, was less in PF and DF than in PC and distal small bowel from fed rabbits (DC) whether expressed per microgram DNA or per intestinal segment. Similarly, thymidine kinase activity was lower in PF and DF than in PC and DC. For both fed and fasted rabbits, more cells were present in the proliferative zone from proximal small bowel than in that from distal. Small bowel labeling index was less in PC than in DC, and less in DF than in DC. The ratio of the number of cells in the proliferative zone to the number of cells in crypt was greater in PC than in DC and greater in DF than in DC. The migration zone was significantly greater in PC than in PF and greater in the fed group in the proximal small bowel than in the distal small bowel. Thus, a 72-h fast in neonatal animals resulted in decreased DNA synthesis and cell migration. Regional alterations in cell proliferation occurred.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Short-term malnutrition in neonatal rabbits: effect on gastrointestinal epithelial proliferation. 272 27

To investigate the effect of chronic protein-calorie malnutrition on intestinal repair after an enteric infection, we examined small intestinal structure, enzyme activity, and sodium transport in undernourished piglets during the acute and convalescent phases of a viral enteritis, transmissible gastroenteritis (TGE). Gnotobiotic pigs, nutritionally deprived from the age of 7 days, gained less weight than dietary controls from 14 days of age until the end of the study. Animals from malnourished and control diet groups were inoculated with TGE virus at 22-23 days and studied during the acute (40 h) and convalescent (4, 10, and 15 days) stages of this experimental enteritis along with noninfected dietary controls. After TGE infection, we observed a further decrease in weight gain and an increased mortality only in undernourished pigs. In jejunum and ileum of both dietary groups at 40 h after TGE infection, we observed comparable structural lesions, similar decreased activities of mucosal enzymes (sucrase, lactase, sodium-potassium-dependent ATPase), and increased thymidine kinase activities. Also we noted comparable diminution of glucose-stimulated jejunal sodium absorption in both dietary groups at 40 h. In control diet pigs, transport abnormalities recovered by 4 days after TGE infection and normal mucosal structure and enzyme activity returned over 4-15 days. In undernourished piglets, structural repair and enzyme abnormalities were prolonged when compared with the control diet group; glucose-stimulated sodium transport did not recover until 10 days after infection and never regained the enhanced activity seen in noninfected undernourished controls.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Impact of chronic protein-calorie malnutrition on small intestinal repair after acute viral enteritis: a study in gnotobiotic piglets. 392 24

The stimulation of intestinal adenylate cyclase by cholera toxin (CT) was studied in normal and malnourished rats 4 to 24 hr after a 30-min incubation of intestinal loops with the toxin. Whereas in control rats the enzyme activity returned to basal levels after 12 hr of incubation, in malnourished rats the activity of the enzyme remained significantly elevated even after 24 hr of the initial incubation. Malnourished animals had a reduced turnover rate of intestinal cells as determined by thymidine kinase activity. The delayed turnover of intoxicated cells may account for continuous activation of mucosal adenylate cyclase and possibly for prolongation of diarrhea in malnutrition.
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PMID:Stimulation of intestinal adenylate cyclase by cholera toxin in malnourished rats. 393 Oct 85

During the past two decades, the essentiality of zinc for man has been established. Deficiency of zinc in man due to nutritional factors and several diseased states has been recognized. High phytate content of cereal proteins decreases availability of zinc; thus the prevalence of zinc deficiency is likely to be high in a population subsisting mainly on cereal proteins. Alcoholism is known to cause hyperzincuria and thus may play a role in producing zinc deficiency in man. Malabsorption, cirrhosis of the liver, chronic renal disease and other chronically debilitating diseases may similarly induce zinc deficiency in human subjects. A severe deficiency of zinc has recently been recognized to occur in patients with sickle cell anemia and a beneficial effect of zinc therapy in such patients has been reported. Growth retardation, male hypogonadism, skin changes, poor appetite, mental lethargy and delayed wound healing are some of the manifestations of chronically zinc-deficient human subjects. Taste abnormalities, correctable with zinc supplementation, have been observed in uremic subjects. Recently, abnormal dark adaptation related to zinc deficiency in patients with cirrhosis of the liver and sickle cell disease has been reported. In severely zinc-deficient patients, dermatological manifestations, diarrhea, alopecia, mental disturbances and intercurrent infections predominate and if untreated the condition becomes fatal. Zinc deficiency is known to affect testicular functions adversely in man and animals. This effect of zinc is at the end organ level and it appears that zinc is essential for spermatogenesis and testosterone steroidogenesis. Zinc is involved in many biochemical functions. Several zinc metalloenzymes have been recognized in the past decade. Zinc is required for each step of cell cycle in microorganisms and is essential for DNA synthesis. Thymidine kinase, RNA polymerase, DNA-polymerase from various sources and RNA-dependent DNA polymerase from viruses have been shown to be zinc-dependent enzymes. Zinc also regulates the activity of RNase; thus the catabolism of RNA appears to be zinc-dependent. The effect of zinc on protein synthesis may be attributable to its vital role in nucleic acid metabolism. The activities of many zinc-dependent enzymes have been shown to be affected adversely in zinc-deficient tissues. Three enzymes, alkaline phosphatase, carboxypeptidase and thymidine kinase, appear to be most sensitive to zinc restriction in that their activities are affected adversely within three to six days of institution of a zinc-deficient diet to experimental animals.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Zinc deficiency in human subjects. 636 78

Wild type Friend erythroleukaemia cells (clone 707) and thymidine kinase (EC. 2.7.1.2.1) deficient derivatives were examined for sensitivity to killing by ultra-violet (UV) irradiation. Deficiency of thymidine kinase leads to increased cell killing as evidenced in all of twelve thymidine kinase deficient clones examined. A revertant thymidine kinase positive clone was found to have a level of thymidine kinase activity and UV sensitivity intermediate between wild type cells and its thymidine kinase deficient parent clone. The increased cell killing in thymidine kinase deficient clones is also reflected in increased mutagenesis by UV to 6-thioguanine resistance. It is suggested that the increased mutagenesis and sensitivity is due to defective DNA repair as a result of an imbalance in deoxyribonucleoside triphosphate pools in thymidine kinase deficient cells.
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PMID:UV sensitivity in thymidine kinase deficient mouse erythroleukaemia cells. 694 58

We studied jejunal epithelial structure and function in rats 24, 48, 96, and 192 hours after a single intravenous injection of methotrexate (MTX) 30 mg/kg. The acute effect of the drug on the gut at 24 and 48 hours was characterised, as expected, by reduced mitoses in crypts, shortened villi, and depressed activity of thymidine kinase (an enzyme normally confined to intestinal crypt cells). At 96 hours, when MTX was no longer detectable in serum, the intestine had entered a proliferative phase characterised by increased crypt mitoses, accelerated migration of enterocytes along villi, and the presence on villi of epithelial cells with the enzyme profile of crypt cells, decreased disaccharidase, alkaline phosphatase, and Na+-K+ATPase activities and increased thymidine kinase activity. Although the enzyme data suggested that enterocyte maturation was defective during this proliferative phase, glucose-stimulated Na+ transport, normally a function of fully differentiated villus cells, was normal at 96 hours. Measured both in Ussing chambers and in suspensions of enterocytes isolated from villi, Na+ transport responded normally to glucose at 96 hours, although the response had been significantly depressed at 24 hours. These findings cannot be attributed to MTX-induced malnutrition, as all comparisons included pair-fed controls. We conclude that, in the MTX-induced malnutrition, as all comparisons included pair-fed controls. We conclude that, in the small intestine under conditions of altered epithelial renewal, some components of enterocyte function may be affected more than others. Comparing the present experimental model with another intestinal disorder, acute viral enteritis, in which proliferative activity is excessive, it is clear that the nature of the original intestinal injury is a significant determinant of the pattern of enterocyte response.
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PMID:Response of the rat small-intestine epithelium to methotrexate. 742 11

The majority of primary bladder neoplasms are known to arise within the mucosa around the ureteric orifices and bladder base. This may be due to the mucosa in this area being more susceptible to carcinogens than other areas of the bladder. Deficiency in the nucleotide salvage pathway enzyme thymidine kinase (TK), and especially its TK1 isozyme, has been shown to predispose cell lines to increased mutagenesis. Total TK and TK1 activities were measured in mucosal samples taken adjacent to the ureteric orifices and dome in 32 normal bladders and both total TK and TK1 were shown to be significantly decreased in the mucosa adjacent to the ureteric orifices. This may explain why primary bladder neoplasms occur more commonly in this site.
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PMID:Why do most primary bladder neoplasms first appear around the ureteric orifices? 843 34

Nutritional deficiency of zinc is widespread throughout developing countries, and zinc-deficient persons have increased susceptibility to a variety of pathogens. Zinc deficiency in an experimental human model caused an imbalance between Th1 and Th2 functions. Production of interferon-gamma and interleukin (IL)-2 (products of Th1) were decreased, whereas production of IL-4, IL-6, and IL-10 (products of Th2) were not affected during zinc deficiency. Zinc deficiency decreased natural killer cell lytic activity and percentage of precursors of cytolytic T cells. In HuT-78, a Th0 cell line, zinc deficiency decreased gene expression of thymidine kinase, delayed cell cycle, and decreased cell growth. Gene expression of IL-2 and IL-2 receptors (both alpha and beta) and binding of NF-kappaB to DNA were decreased by zinc deficiency in HuT-78. Decreased production of IL-2 in zinc deficiency may be due to decreased activation of NF-kappaB and subsequent decreased gene expression of IL-2 and IL-2 receptors.
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PMID:Effects of zinc deficiency on Th1 and Th2 cytokine shifts. 1094 85

Deficiency of mitochondrial thymidine kinase (TK2) is associated with mitochondrial DNA (mtDNA) depletion and manifests by severe skeletal myopathy in infancy. In order to elucidate the pathophysiology of this condition, mitochondrial deoxyribonucleoside triphosphate (dNTP) pools were determined in patients' fibroblasts. Despite normal mtDNA content and cytochrome c oxidase (COX) activity, mitochondrial dNTP pools were imbalanced. Specifically, deoxythymidine triphosphate (dTTP) content was markedly decreased, resulting in reduced dTTP:deoxycytidine triphosphate ratio. These findings underline the importance of balanced mitochondrial dNTP pools for mtDNA synthesis and may serve as the basis for future therapeutic interventions.
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PMID:Mitochondrial deoxyribonucleoside triphosphate pools in thymidine kinase 2 deficiency. 1455 Feb 98

Deficiency of thymidine kinase-2 (TK2) has been described in children with early onset fatal skeletal myopathy. TK2 is a mitochondrial deoxyribonucleoside kinase required for the phosphorylation of deoxycytidine and deoxythymidine and hence is vital for the maintenance of a balanced mitochondrial dNTP pool in post-mitotic tissues. We describe a patient with two novel TK2 mutations, which caused disease onset shortly after birth and death at the age of three months. One mutation (219insCG) generated an early stop codon, thus preventing the synthesis of a functional protein. The second mutation (R130W) resulted in an amino acid substitution, which caused a severe reduction (<3%) of TK2 enzyme activity. These two novel TK2 mutations cause an extremely severe phenotype with overwhelming central nervous system symptoms not commonly seen in patients with TK2-deficiency. We conclude that the severe clinical presentation in this patient was due to a virtual lack of mitochondrial TK2 activity.
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PMID:Two novel mutations in thymidine kinase-2 cause early onset fatal encephalomyopathy and severe mtDNA depletion. 2008 5


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