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Published on: October 15, 2018
Complex changes in ecto-nucleoside 5'-triphosphate diphosphohydrolase expression in hypoxanthine phosphoribosyl
Veronika Lorenz1, Cibele S Pinto, Roland Seifert
1Department of Pharmacology and Toxicology, University of Regensburg, Germany.
Neuroscience Letters
|April 27, 2007
Summary
Lesch-Nyhan disease, caused by hypoxanthine phosphoribosyl transferase (HPRT) deficiency, affects ecto-nucleoside triphosphate diphosphohydrolase (NTPDase) expression. These complex changes in NTPDase levels may represent cellular compensation for altered nucleotide metabolism.
Area of Science:
- Biochemistry
- Neuroscience
- Genetics
Background:
- Lesch-Nyhan disease results from a deficiency in the purine salvage enzyme hypoxanthine phosphoribosyl transferase (HPRT).
- The precise mechanism linking HPRT deficiency to the disease's characteristic neuropsychiatric symptoms remains unclear.
- Altered nucleoside 5'-triphosphatase (NTPase) activity has been observed in cellular models of HPRT deficiency.
Purpose of the Study:
- To investigate the expression patterns of ecto-nucleoside triphosphate diphosphohydrolases (NTPDases) in cellular models of HPRT deficiency.
- To determine if changes in NTPDase expression correlate with altered NTPase activity observed in Lesch-Nyhan disease.
- To explore potential compensatory mechanisms in nucleotide metabolism.
Main Methods:
- Reverse transcriptase polymerase chain reaction (RT-PCR) was employed to analyze NTPDase gene expression.
- Restriction enzyme digestion of amplified cDNA fragments was used to differentiate between NTPDase isoforms.
- Studies were conducted on rat B103 neuroblastoma cells, mouse Neuro2a neuroblastoma cells, and fibroblasts from HPRT knock-out mice.
Main Results:
- HPRT deficiency led to decreased expression of NTPDases 1, 3, and 6, and increased expression of NTPDases 4 and 5 in B103 cells.
- In Neuro2a cells, HPRT deficiency resulted in increased expression of NTPDases 3, 4, 5, and 6.
- Fibroblasts from HPRT knock-out mice showed decreased NTPDase 3 expression and increased expression of NTPDases 4, 5, and 6.
Conclusions:
- HPRT deficiency causes complex, cell-type and species-specific alterations in NTPDase isoform expression.
- These observed changes in NTPDase expression may indicate an cellular attempt to adapt to the metabolic disturbances caused by HPRT deficiency.
- Further research is needed to elucidate the functional consequences of these NTPDase expression changes in the context of Lesch-Nyhan disease pathophysiology.
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