Effect of hypoxia on purine metabolism in human skeletal muscle cells
Abstract Mammals experience some degree of hypoxia during their lifetime. In response to hypoxic challenge, mammalian cells orchestrate specific responses at transcriptional and posttranslational level, which lead to changes in purine metabolites in order to cope with threatening conditions. The aim of this study was to evaluate the response of the enzymes involved in purine metabolism at human muscle cells under hypoxic conditions. Muscle cells in culture were exposed to hypoxia and the enzymatic activity of inosine monophosphate dehydrogenase (IMPDH), xanthine oxidase (XO), purine nucleoside phosphorylase (PNP) and hypoxanthine guanine phosphoribosyl transferase (HGPRT) as well as their transcript expression were quantified under normoxic and hypoxic conditions. Purine metabolite (hypoxanthine (HX), xanthine (X), uric acid (UA), inosine monophosphate (IMP), inosine, nicotinamide adenine dinucleotide (NAD+), adenosine, adenosine monophosphate (AMP), adenosine diphosphate (ADP), adenosine triphosphate (ATP), guanosine diphosphate (GDP) and guanosine triphosphate (GTP)) concentrations were also quantified. Significant reduction of IMPDH activity as well as in HX and IMP concentrations (p < 0.05) were observed after hypoxia, suggesting a decrease in the purines de novo synthesis. After hypoxia a global reduction of transcripts was observed, suggesting a reduction of the metabolic machinery of purine metabolism to new steady states that balance ATP demand and ATP supply pathways.
| Main Authors: | , , , , , |
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| Format: | Digital revista |
| Language: | English |
| Published: |
Universidad de Sonora, División de Ciencias Biológicas y de la Salud
2021
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| Online Access: | http://www.scielo.org.mx/scielo.php?script=sci_arttext&pid=S1665-14562021000200141 |
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