Changes in cardiac nucleotide metabolism in Huntington's disease

Autor:	Paulina Zukowska, Michal Mielcarek, Marta Toczek, Ryszard T. Smolenski, Mark Isalan, Barbara Kutryb-Zajac, Ewa M. Slominska
Přispěvatelé:	Commission of the European Communities
Rok vydání:	2016
Předmět:	0301 basic medicine Adenosine Adenosine Deaminase Cardiomyopathy Biochemistry AMP Deaminase 03 medical and health sciences Mice Adenosine deaminase Huntington's disease Adenine nucleotide Genetics medicine Animals Humans Nucleotide Pyrophosphatases chemistry.chemical_classification biology adenine nucleotides catabolism Myocardium Organic Chemistry 0601 Biochemistry And Cell Biology AMP deaminase General Medicine Metabolism medicine.disease Molecular biology Inosine Disease Models Animal 030104 developmental biology Enzyme Huntington Disease chemistry HD-related cardiomyopathy Purine-Nucleoside Phosphorylase biology.protein Molecular Medicine
Zdroj:	Nucleosides, nucleotidesnucleic acids. 35(10-12)
ISSN:	1532-2335
Popis:	Huntington's disease (HD) is a monogenic neurodegenerative disorder with a significant peripheral component to the disease pathology. This includes an HD-related cardiomyopathy, with an unknown pathological mechanism. In this study, we aimed to define changes in the metabolism of cardiac nucleotides using the well-established R6/2 mouse model. In particular, we focused on measuring the activity of enzymes that control ATP and other adenine nucleotides in the cardiac pool, including eNTPD, AMPD, e5'NT, ADA, and PNP. We employed HPLC to assay the activities of these enzymes by measuring the concentrations of adenine nucleotide catabolites in the hearts of symptomatic R6/2 mice. We found a reduced activity of AMPD (12.9 ± 1.9 nmol/min/mg protein in control; 7.5 ± 0.5 nmol/min/mg protein in R6/2) and e5'NT (11.9 ± 1.7 nmol/min/mg protein in control; 6.7 ± 0.7 nmol/min/mg protein in R6/2). Moreover, we detected an increased activity of ADA (1.3 ± 0.2 nmol/min/mg protein in control; 5.2 ± 0.5 nmol/min/mg protein in R6/2), while no changes in eNTPD and PNP activities were observed. Analysis of cardiac adenine nucleotide catabolite levels revealed an increased inosine level (0.7 ± 0.01 nmol/mg dry tissue in control; 2.7 ±0.8 nmol/mg dry tissue in R6/2) and a reduced concentration of cardiac adenosine (0.9 ± 0.2 nmol/mg dry tissue in control; 0.2 ± 0.08 nmol/mg dry tissue in R6/2). This study highlights a decreased rate of degradation of cardiac nucleotides in HD mouse model hearts, and an increased capacity for adenosine deamination, that may alter adenosine signaling.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9e29e0c21a5df73259a7bc598ddaf356 https://pubmed.ncbi.nlm.nih.gov/27906632 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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