Pinto, C. S. and Jinnah, H. A. and Shirley, T. L. and Nyhan, W. L. and Seifert, Roland (2005) Altered membrane NTPase activity in Lesch-Nyhan disease fibroblasts: comparison with HPRT knockout mice and HPRT-deficient cell lines. JOURNAL OF NEUROCHEMISTRY, 93 (6). pp. 1579-1586. ISSN 0022-3042, 1471-4159
Full text not available from this repository. (Request a copy)Abstract
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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GENETIC MOUSE MODEL; PHOSPHORIBOSYLTRANSFERASE-DEFICIENCY; DISTINCT INTERACTIONS; TRANSGENIC MICE; PURINE; NEUROBLASTOMA; METABOLISM; GTP; G(S-ALPHA-SHORT); 5'-NUCLEOTIDASE; B103 neuroblastoma cells; fibroblasts; Lesch-Nyhan disease; Neuro-2a neuroblastoma cells; NTPase |
| Subjects: | 600 Technology > 615 Pharmacy |
| Divisions: | Chemistry and Pharmacy > Institute of Pharmacy > Pharmacology and Toxicology (Prof. Schlossmann, formerly Prof. Seifert) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 11 May 2021 08:52 |
| Last Modified: | 11 May 2021 08:52 |
| URI: | https://pred.uni-regensburg.de/id/eprint/36077 |
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