Open AccessEffect of hypoxia on purine metabolism of human skeletal muscle cells
Author(s) -
Tania ZentenoSavín,
Crisalejandra Rivera-Pérez,
Ramón Gaxiola-Robles,
Norma O. OlguínMonroy,
Orlando Lugo-Lugo,
Roberto I. LópezCruz
Publication year - 2021
Publication title -
biotecnia
Language(s) - English
Resource type - Journals
ISSN - 1665-1456
DOI - 10.18633/biotecnia.v23i2.1444
Subject(s) - hypoxanthine , inosine , purine nucleoside phosphorylase , purine metabolism , biochemistry , inosine monophosphate , purine , guanosine , adenosine , adenosine monophosphate , xanthine , xanthine dehydrogenase , adenosine triphosphate , chemistry , hypoxanthine guanine phosphoribosyltransferase , xanthine oxidase , biology , enzyme , nucleotide , gene , mutant
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 the purine metabolites in order to cope with threatening conditions. The aim of this study was to evaluate the response of the enzymes involved in the purine metabolism of human muscle cells to 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 and HX and IMP concentrations (p < 0.05) were observed after hypoxia, suggesting a decrease of de novo synthesis of purines. 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.