Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.6.1.3 (ATPase)
 65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hybrid cell clones between mouse cells deficient in thymidine kinase (EC 2.7.1.21) and two different human cell lines transformed by simian virus 40 (SV40) and deficient in hypoxanthine phosphoribosyltransferase (EC 2.4.2.8) were examined for SV40 tumor (T) antigen(s). Concordant segregation of the gene(s) for SV40 T antigen and human chromosome C-7 was observed in these hybrids. The human chromosome C-7 which contains the gene(s) for SV40 T antigen is preferentially retained by the majority of the hybrid clones tested. When hybrid clones positive and negative for SV40 T antigen, derived from the fusion of SV40-transformed Lesch-Nyhan fibroblasts with mouse cells, were fused with CV-1 permissive cells, SV40-specific V antigen was observed only in the cultures derived from fusion of the hybrid clones positive for T antigen. This result indicates a linkage relationship between human chromosome C-7, SV40 T-antigen gene(s), and SV40 genome(s) integrated in the human transformed cells.
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PMID:Assignment of the T-antigen gene of simian virus 40 to human chromosome C-7. 435 83

Skin fibroblasts of three Lesch-Nyhan patients were successfully transformed to unrestricted growth by Simian virus 40. The transformed character of isolated clones was confirmed by their epitheloid growth in medium containing low concentration of serum, by hyperdiploid karyotype patterns, by detection of SV40 T-antigen, by their growth in soft agar and by the proliferation of cells in vitro up to 200 passages hitherto.
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PMID:Immortalization of human Lesch-Nyhan-fibroblasts following infection with Simian virus 40. 630 4

In the present study, we investigated the in vitro effect of hypoxanthine, xanthine and uric acid, metabolites accumulating in tissue of patients with Lesch-Nyhan disease, on Na(+), K(+)-ATPase activity in striatum of neonate rats. Results showed that all compounds significantly inhibited Na(+), K(+)-ATPase activity. We also studied the kinetics of the inhibition of Na(+), K(+)-ATPase activity caused by hypoxanthine. The apparent K(m) and V(max) of Na(+), K(+)-ATPase activity for ATP as the substrate and hypoxanthine as the inhibitor were 0.97 mM and 0.69 nmol inorganic phosphate (Pi) released per min per mg of protein, respectively. K(i)-value was 1.9 microM, and the inhibition was of the non-competitive type. We also observed that the inhibitory effects of hypoxanthine, xanthine and uric acid probably occur through the same mechanism, suggesting a common binding site for these oxypurines on Na(+), K(+)-ATPase. Therefore, it is conceivable that inhibition of brain Na(+), K(+)-ATPase activity may be involved at least in part in the neuronal dysfunction characteristic of patients with Lesch-Nyhan disease.
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PMID:Inhibition of Na+, K+-ATPase activity in rat striatum by the metabolites accumulated in Lesch-Nyhan disease. 1501 74

The main objective of this study was to investigate the effects of preincubation of rat striatum homogenate in the presence of hypoxanthine, a metabolite accumulated in Lesch-Nyhan disease, on Na+,K+-ATPase activity and on some parameters of oxidative stress namely thiobarbituric acid-reactive substances (TBA-RS), total radical-trapping antioxidant parameter (TRAP) and membrane protein thiol content. Results showed that hypoxanthine significantly increased TBA-RS and reduced Na+,K+-ATPase activity, TRAP and membrane protein thiol content. In addition, we also evaluated the effect of glutathione, trolox, allopurinol and Nvarpi-nitro-L-arginine methyl ester (L-NAME) on the inhibitory effect of hypoxanthine on Na+,K+-ATPase activity in the same rat cerebral structure. All tested compounds per se did not alter Na+,K+-ATPase activity, but only glutathione and trolox prevented the effect of hypoxanthine on the enzyme activity. The effect of glutathione and trolox on hypoxanthine-induced increase of TBA-RS levels was also investigated. These antioxidants alone or combined with hypoxanthine reduced TBA-RS levels. Our present findings show that hypoxanthine induces oxidative stress in rat striatum and that the inhibition of Na+,K+-ATPase activity caused by this oxypurine was probably mediated by reactive oxygen species. It is presumed that these results might be associated with the neuronal dysfunction of patients affected by Lesch-Nyhan disease.
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PMID:Effect of hypoxanthine on Na+,K+-ATPase activity and some parameters of oxidative stress in rat striatum. 1582 28

Lesch-Nyhan disease (LND) is a rare disorder caused by a defect of an enzyme in the purine salvage pathway, hypoxanthine phosphoribosyl transferase (HPRT). It is still unknown how the metabolic defect translates into the complex neuropsychiatric phenotype characterized by self-injurious behavior, dystonia and mental retardation. There are abnormalities in purine and pyrimidine nucleotide content in HPRT-deficient cells. We hypothesized that altered nucleotide concentrations in HPRT deficiency change G-protein-mediated signal transduction. Therefore, our original study aim was to examine the high-affinity GTPase activity of G-proteins in membranes from primary human skin and immortalized mouse skin fibroblasts, rat B103 neuroblastoma cells and mouse Neuro-2a neuroblastoma cells. Unexpectedly, in membranes from human fibroblasts, B103- and Neuro-2a cells, V(max) of low-affinity nucleoside 5'-triphosphatase (NTPase) activities was decreased up to 7-fold in HPRT deficiency. In contrast, in membranes from mouse fibroblasts, HPRT deficiency increased NTPase activity up to 4-fold. The various systems analyzed differed from each other in terms of K(m) values for NTPs, absolute V(max) values and K(i) values for nucleoside 5'-[beta,gamma-imido]triphosphates. Our data show that altered membrane NTPase activity is a biochemical hallmark of HPRT deficiency, but species and cell-type differences have to be considered. Thus, future studies on biochemical changes in LND should be conducted in parallel in several HPRT-deficient systems.
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PMID:Altered membrane NTPase activity in Lesch-Nyhan disease fibroblasts: comparison with HPRT knockout mice and HPRT-deficient cell lines. 1593 74

The aim of this study was to investigate the effects of a single intrastriatal injection of hypoxanthine, the major metabolite accumulating in Lesch-Nyhan disease, on Na(+),K(+)-ATPase, acetylcholinesterase and catalase activities in striatum, cerebral cortex and hippocampus of rats at different post-infusion periods. Adult Wistar rats were divided in two groups: (1) vehicle-injected group (control) and (2) hypoxanthine-injected group. For Na(+),K(+)-ATPase activity determination, the animals were sacrificed 3h, 24h and 7 days after drug infusion. For the evaluation of acetylcholinesterase and catalase activities, the animals were sacrificed 30min, 3h, 24h and 7 days after hypoxanthine infusion. Results show regional and time dependent effects of hypoxanthine on Na(+),K(+)-ATPase, acetylcholinesterase and catalase activities. The in vitro effect of hypoxanthine on the same enzymes in striatum was also investigated. Results showed that hypoxanthine inhibited Na(+),K(+)-ATPase, but not the activities of acetylcholinesterase and catalase in rat striatum. We suggest that these modification on cerebral biochemical parameters (Na(+),K(+)-ATPase, acetylcholinesterase and catalase activities) induced by intrastriatal administration of hypoxanthine in all cerebral structures studied, striatum, hippocampus and cerebral cortex, could be involved in the pathophysiology of Lesch-Nyhan disease.
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PMID:Intrastriatal hypoxanthine administration affects Na+,K+-ATPase, acetylcholinesterase and catalase activities in striatum, hippocampus and cerebral cortex of rats. 1703 84

Lesch-Nyhan disease is caused by a deficiency of the purine salvage enzyme, hypoxanthine phosphoribosyl transferase (HPRT). The link between HPRT deficiency and the neuropsychiatric symptoms is unknown. In rat B103 neuroblastoma cell membranes and mouse Neuro2a neuroblastoma cell membranes, nucleoside 5'-triphosphatase (NTPase) activity is substantially reduced, whereas in fibroblast membranes from HPRT knock-out mice, NTPase activity is increased. Candidate genes for these NTPase activity changes are ecto-nucleoside 5'-triphosphate diphosphohydrolases (NTPDases). Therefore, we studied expression of NTPDases in B103 cells, Neuro2a cells and skin fibroblasts by reverse transcriptase polymerase chain reaction and restriction enzyme digestion of amplified cDNA fragments. In B103 cells, expression of NTPDases 1, 3 and 6 decreased, whereas expression of NTPDases 4 and 5 increased in HPRT deficiency. In Neuro2a cells, expression of NTPDases 3-6 increased in HPRT deficiency. In fibroblasts, NTPDase 3 expression decreased, and expression of NTPDases 4-6 increased in HPRT deficiency. Collectively, there are complex decreases and increases in NTPDase isoform expression in HPRT deficiency that depend on the specific cell type and species studied. These changes in NTPDase expression may reflect an (insufficient) attempt of cells to compensate for the changes in nucleotide metabolism caused by HPRT deficiency.
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PMID:Complex changes in ecto-nucleoside 5'-triphosphate diphosphohydrolase expression in hypoxanthine phosphoribosyl transferase deficiency. 1745 84

We previously demonstrated that intrastriatal injection of hypoxanthine, the major metabolite accumulating in Lesch-Nyhan disease, inhibited Na+,K+-ATPase activity and induced oxidative stress in rat striatum. In the present study, we evaluated the action of vitamins E and C on the biochemical alteration induced by hypoxanthine administration on Na+,K+-ATPase, TBARS, TRAP, as well as on superoxide dismutase (SOD), catalase (CAT) and glutathione-peroxidase (GPx) activities in striatum of adult rats. Animals received pretreatment with vitamins E and C or saline during 7 days. Twelve hours after the last injection of vitamins or saline, animals were divided into two groups: (1) vehicle-injected group and (2) hypoxanthine-injected group. For all parameters investigated in this research, animals were sacrificed 30 min after drug infusion. Results showed that pretreatment with vitamins E and C prevented hypoxanthine-mediated effects on Na+,K+-ATPase, TBARS and antioxidant enzymes (SOD, CAT and GPx) activities; however the reduction on TRAP was not prevented by these vitamins. Although extrapolation of findings from animal experiments to humans is difficult, it is conceivable that these vitamins might serve as an adjuvant therapy in order to avoid progression of striatal damage in patients affected by Lesch-Nyhan disease.
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PMID:Biochemical effects of pretreatment with vitamins E and C in rats submitted to intrastriatal hypoxanthine administration. 1829 33