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Hypoxia decreases creatine transport in cardiomyocytes and C2C12 cells
Author(s) -
Arciniegas Jose,
Jacobs Danny O.,
Santacruz Lucia
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1033.11
Subject(s) - c2c12 , hypoxia (environmental) , myocyte , creatine , chemistry , medicine , microbiology and biotechnology , biology , oxygen , myogenesis , organic chemistry
Creatine (Cr) and Phosphocreatine (PCr) are components of an energy buffering system in skeletal and cardiac muscle and brain. Cr oral supplementation is commonly used by athletes and may also have therapeutic value in the treatment of Duchenne's disease, inflammatory myopathies, Parkinson's‐, Huntington's‐, Alzheimer's disease, and Cr synthesis deficiency syndromes. Myocytes lack Cr biosynthethic capabilities and depend on Na + /Cl − ‐dependent transporter (CrT), to maintain their intracellular Cr content. Hypoxia alters energy homeostasis, decreasing Cr kinase activity, PCr and ATP levels. However, its effects on Cr transport are not known. Rat neonatal cardiomyocytes (RNCM) and C2C12 cells were used to characterize myocellular 14 C‐Cr uptake following hypoxia. Hypoxia was achieved by placing the cells in a sealed chamber with a 5% CO2, N 2 balanced atmosphere with an O 2 <1%. Activation of the cellular hypoxic response was validated using an HRE‐AAV (Hypoxia Response Elements Adeno Associated Virus)‐luciferase reporter system. In RNCM and C2C12 cells, hypoxia causes a time dependent decrease in Cr transport. 1 hr of hypoxia reduced Cr transport by 15%, with 14 C‐Cr uptake falling to 70% of control values after 24 hrs of hypoxia. Our results suggest that a reduction in Cr transport contributes to the energy homeostasis alterations observed in hypoxic skeletal and cardiac muscle.