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)

Aging of IMR-90 human diploid fibroblasts in vitro is accompanied by significant changes of polyamine metabolism, most notably, a 5-fold decrease of serum-induced activity of ornithine decarboxylase, the key enzyme in the biosynthesis of polyamines (Chen, K. Y., Chang, Z. F., and Liu, A. Y.-C. (1986) J. Cell. Physiol. 129, 142-146). In this paper, we employed Northern blot hybridization and affinity radiolabeling techniques to investigate the molecular basis of this age-associated change of ornithine decarboxylase activity. Since the induction of ornithine decarboxylase by serum is a mid-G1 event, we also examined expressions of other cell cycle-dependent genes that are induced before and after the mid-G1 phase to determine if their expressions may also be age-dependent. Our results demonstrated a 3-fold decrease of the amount of active ornithine decarboxylase molecules that can be labeled by alpha-difluoromethyl[3H]ornithine in senescent IMR-90 cells (population doubling level (PDL) = 52) as compared to young cells (PDL = 22). However, the levels and kinetics of induction of ornithine decarboxylase mRNA in both young and senescent IMR-90 cells were found to be identical throughout a 24-h time period after serum stimulation. The time course and the magnitude of the expression of c-myc, an early G1 gene, were quite similar in young and senescent IMR-90 cells and appeared to be PDL-independent. In contrast, the expression of thymidine kinase, a late G1/S gene, was significantly reduced in senescent IMR-90 cells. Levels of thymidine kinase mRNA and thymidine kinase activity in senescent IMR-90 cells were 6- and 8-fold less than those in young cells, respectively. Based on these data, we proposed that impairment of cell cycling in senescent IMR-90 cells may occur at the late G1/S phase and that decreases of ornithine decarboxylase activity and putrescine accumulation during cell senescence may contribute to this impairment.
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PMID:Regulation of ornithine decarboxylase and other cell cycle-dependent genes during senescence of IMR-90 human diploid fibroblasts. 340 38

The nature of the growth-stimulating effect of glucosylceramide was studied. Mice were injected intraperitoneally with emulsified glucosylceramide and conduritol B epoxide, an inhibitor of cerebroside glucosidase. Within one or two days, the liver grew 18-24%, as reported. Two enzymes involved in DNA synthesis also increased more than the weight. The total liver activity of thymidine kinase increased 46-73%, and the total activity of ornithine decarboxylase increased as much as 101%. It is suggested that elevated liver levels of glucocerebroside stimulate cell proliferation through a relatively direct mechanism.
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PMID:Stimulation of liver growth and DNA synthesis by glucosylceramide. 341 33

Orthotopic liver transplantation was performed in two groups of dogs; Group I animals consisted of large dogs that served as recipients of livers obtained from smaller dogs while Group II animals consisted of dogs that received liver from donor dogs of nearly the same size. The small-for-size livers transplanted into the Group I dogs rapidly increased in size over the course of 2 weeks until they achieved a size equal to that originally present in the larger recipient dogs. In contrast, the livers transplanted into dogs of the same size as the donors underwent some degree of atrophy. In both groups of animals, plasma levels of insulin and glucagon and hepatic (graft) activities of thymidine kinase and ornithine decarboxylase were followed serially. The only difference between the two groups of animals for these measures was that the ornithine decarboxylase activity rose to a greater degree in the liver that underwent graft enlargement. These data suggest that recipient size determines, at least in part, liver graft size once it is transplanted. These data also suggest that of the parameters followed, only ornithine decarboxylase activity parallels the finding of growth of the transplanted liver.
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PMID:Evidence that host size determines liver size: studies in dogs receiving orthotopic liver transplants. 354 8

The ability to respond to changes in the external and internal environments is a fundamental characteristic of intestinal structure and function. We compared the responses of the rat proximal and distal small intestine to the stresses of fasting and refeeding in the rat. In the duodenum, 3 days of starvation caused villus and crypt hypoplasia, reduced incorporation of [3H]thymidine into crypt cells, decreased cell migration rate on the villus, and lowered specific and total activities of several cellular enzymes. These changes were reversed by 1 day of refeeding. In contrast, mucosal hypoplasia did not occur in the ileum during fasting, and the specific activities of the disaccharidases were increased after 3 days of starvation. However, ileal [3H]thymidine incorporation, thymidine kinase activity, and ornithine decarboxylase activity decreased during starvation. These effects were also reversed by refeeding. The results of these studies illustrate differing responses for the proximal and distal small intestine and suggest the presence of distinctly differing mechanisms for the control of their mucosal mass and enzyme activities.
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PMID:Ileal hyperplastic response to starvation in the rat. 372 71

A previous study has shown that the activity of ornithine decarboxylase in cultured Nb2 node rat lymphoma cells falls to undetectable levels when cells become quiescent following incubation in lactogen (prolactin)-deficient medium. In the present study, it was found that addition of extracts of the lactogen-deprived, quiescent cells to extracts of log-phase cells markedly reduced the ornithine decarboxylase activity of the latter, the inhibitory activity being proportional to the amount of quiescent cell extract added. Evidence is presented that the ornithine decarboxylase-inhibitory activity in the quiescent cell extracts is due to an antizyme-like, polypeptide factor with an Mr of approx. 28,000. The activity of the inhibitor appears to be directed rather specifically against ornithine decarboxylase, since the activities of S-adenosylmethionine decarboxylase, thymidine kinase and uridine kinase were not affected. The Nb2 cell ornithine decarboxylase inhibitor may have an important role in modulating the cellular levels of ornithine decarboxylase as they change in response to the withdrawal and restoration of extracellular mitogenic lactogens.
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PMID:An inhibitor of ornithine decarboxylase in lactogen-deprived Nb2 node rat lymphoma cells. 375 20

Pericentral and periportal liver injuries involving less than 50% of the parenchyma were produced with acetaminophen and allyl alcohol, respectively. Doses were selected to produce comparable peak serum malate dehydrogenase, sorbitol dehydrogenase, and SGPT activities. The regenerative response was assessed by serial measurements of hepatic thymidine kinase (TK) activity and ornithine decarboxylase (ODC) activity. The initial responses reflected in ODC activity were more or less similar. However, the ultimate regenerative response reflected by TK activity was almost three times as great after periportal injury as after pericentral injury, after allowing for differences in the extent of necrosis. Histologic examination also showed greater mitotic and tissue reparative responses after periportal injury. These results suggest that the concept of hepatocellular heterogeneity applies to the regenerative response of liver cells as well as the metabolic functions previously identified.
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PMID:Hepatic regenerative enzyme activity after pericentral and periportal lobular toxic injury. 378 16

To investigate the sequence of events that occur in the liver during mirex-induced adaptive liver growth, [3H]thymidine incorporation into DNA, thymidine kinase (TK), and ornithine decarboxylase (ODC) were studied in intact and adrenalectomized (ADX) mirex-dosed rats, and the responses were compared with experimental groups receiving corticosterone. In intact mirex-dosed rats (a response that is both hyperplastic and hypertrophic) there was a 36-h peak in ODC activity, and a 48-h peak in both [3H]thymidine incorporation into DNA and TK activity. This was accompanied by a 72% increase in relative liver weight (RLW). In contrast, in ADX mirex-dosed rats (a predominately hyperplastic response), there was a biphasic ODC response (18- and 36-h peaks), a 36-h TK peak, and a 48-h peak in [3H]thymidine incorporation into DNA. Both TK activity and [3H]thymidine incorporation into DNA were significantly elevated for the remainder of the 96-h study period. There was a 38% increase in RLW. Corticosterone supplements to mirex-dosed intact rats resulted in a biphasic peak of TK activity (30- and 48-h peaks), a reduced ODC peak at 36 h, and a 48-h peak in [3H]thymidine incorporation into DNA. RLW response was similar to the response in intact mirex-dosed rats. Corticosterone supplements to mirex-dosed ADX rats eliminated the 48-h peak of [3H]thymidine incorporation into DNA, reduced TK activity and shifted the peak to 30 h, and eliminated the ODC biphasic response. The RLW increase was similar to the response in intact mirex-dosed rats with a maximum 80% increase at 72 h postmirex dose.
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PMID:The relationship of ornithine decarboxylase and thymidine kinase to mirex-induced liver growth. 378 52

Four injections of subcoma doses of ammonium acetate, octanoic acid or dimethyl disulfide during the first 24 hr after two-lobe hepatectomy in normal rats markedly depressed DNA synthesis as reflected by liver thymidine kinase activity or the incorporation of tritiated thymidine into hepatic DNA. Recovery from the depressant effects of the three toxins took 16 to 28 hr. Similar doses of the same toxins injected hourly for 3 or 5 hr after the two-lobe hepatectomy had similar depressant effects on the early peak of ornithine decarboxylase activity measured at 4 or 6 hr. Recovery occurred within 3 hr perhaps because of the very short half-life of ornithine decarboxylase and its rapid regeneration time. These observations may have implications for the lack of regeneration observed in many patients with fulminant hepatic failure who have accumulated sufficient ammonia, methanethiol and fatty acids over periods of days or weeks to become encephalopathic.
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PMID:Ammonia, octanoate and a mercaptan depress regeneration of normal rat liver after partial hepatectomy. 396 63

After subtotal (80% to 90%) hepatectomy of the normal rat liver, thymidine kinase activity began to increase after 24 hours and reached a maximum at 36 hours. This persisted for another 60 hours before it declined to reach the baseline by 7 to 8 days. The maximal increase was 30- to 50-fold. After two-lobe (67% to 78%) hepatectomy, the maximal increase was similar, but the onset and the maximum each occurred 12 hours earlier, and the maximum only persisted for another 24 hours. The important first peak of ornithine decarboxylase activity occurred earlier and rose higher after 67% to 78% hepatectomy. The distributions with time of histologic mitosis counts were similar to the distributions of thymidine kinase activity (reflects DNA synthesis) at each of the three levels of hepatectomy, 80% to 90%, 67% to 78% and 37% +/- 0.5%. Thus the initiation of regeneration was delayed after subtotal resection, but the regenerative response as reflected by DNA synthesis and cell multiplication was prolonged.
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PMID:Course of hepatic regeneration after 80% to 90% resection of normal rat liver. Comparison with two-lobe and one-lobe hepatectomy. 397 69

Massive liver injury was produced in fasting male Sprague-Dawley rats weighing 200 +/- 25 gm each by gastric administration of 1400 mg/kg acetaminophen. The time sequence of changes in liver ornithine decarboxylase (ODC) activity, which reflects the earliest phases of cell multiplication, liver thymidine kinase (TK) activity, which reflects DNA synthesis, and liver histology (necrosis, mitosis, and repair processes) was recorded. ODC showed the usual biphasic response. By 12 hours, it reached its first peak, a six- to eightfold increase. At this time there was no histologic evidence of necrosis, and serum malate dehydrogenase (MDH), sorbitol dehydrogenase (SDH), and alanine aminotransferase (SGPT) were normal. During the next 12 hours ODC decreased by 60% to 70% and cellular necrosis became evident, and reached a peak at 24 to 36 hours, as did serum MDH, SDH, and SGPT. The serum enzymes fell precipitously at 48 hours, but the histologic evidence of necrosis subsided gradually over 60 hours. The secondary ODC peak, a fourfold increase, coincided with rising activity of TK, which increased 25- to 35-fold over 54 to 72 hours, and then subsided. At 54 hours, when DNA synthesis had already peaked, there was no histologic evidence of repair other than mitoses. However, within the next 6 hours, evidences of repair became prominent, and remained so for another 36 hours before subsiding. Thus, with acetaminophen injury, the initial phases in preparation for cell multiplication occurred before histologic evidence of injury was apparent, and DNA synthesis peaked before other evidence of tissue repair became evident.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Acetaminophen liver injury: sequential changes in two biochemical indices of regeneration and their relationship to histologic alterations. 398 55


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