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)

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

The hepatoprotective effect of putrescine against cadmium liver injury was investigated. Male Wistar rats were injected with a dose of cadmium (6.5 mg CdCl(2)/kg bodyweight, intraperitoneally). Normal saline (group I) or putrescine (300 micro mol/kg bodyweight; group II) were injected 2, 5 and 8 h later. A number of animals of both groups were killed 0, 12, 16, 24, 48 or 60 h after cadmium intoxication. Liver tissue was histologically assessed for necrosis, apoptosis, peliosis, mitoses, and inflammatory infiltration. Apoptosis was also quantified by the TUNEL assay for hepatocytes and nonparenchymal liver cells. The discrimination between hepatic cell subpopulations was achieved histochemically. The mitotic index in hematoxylin-eosin-stained sections and by the immunochemical detection of Ki67 nuclear antigen, (3)H-thymidine incorporation into hepatic DNA, and hepatic thymidine kinase activity were all used as indices of liver regeneration. Both hepatocyte apoptosis and liver necrosis evolved in a biphasic temporal pattern. Nonparenchymal cell apoptosis and peliosis hepatis evolved in a monophasic pattern and were correlated closely. Putrescine administration totally reversed liver necrosis and hepatocyte apoptosis. The time profile of nonparenchymal apoptosis was altered and peliosis hepatis was also totally attenuated. In conclusion, putrescine protected hepatocytes and modulated the mechanism of cadmium-induced acute hepatotoxicity.
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PMID:The hepatoprotective effect of putrescine against cadmium-induced acute liver injury. 1500 64