Creatine Prevents the Structural and Functional Damage to Mitochondria in Myogenic, Oxidatively Stressed C2C12 Cells and Restores Their Differentiation Capacity.
Creatine (Cr) is a nutritional supplement promoting a number of health benefits. Indeed Cr has been shown to be beneficial in disease-induced muscle atrophy, improve rehabilitation, and afford mild antioxidant activity. The beneficial effects are likely to derive from pleiotropic interactions. In accord with this notion, we previously demonstrated that multiple pleiotropic effects, including preservation of mitochondrial damage, account for the capacity of Cr to prevent the differentiation arrest caused by oxidative stress in C2C12 myoblasts. Given the importance of mitochondria in supporting the myogenic process, here we further explored the protective effects of Cr on the structure, function, and networking of these organelles in C2C12 cells differentiating under oxidative stressing conditions; the effects on the energy sensor AMPK, on PGC-1α, which is involved in mitochondrial biogenesis and its downstream effector Tfam were also investigated. Our results indicate that damage to mitochondria is crucial in the differentiation imbalance caused by oxidative stress and that the Cr-prevention of these injuries is invariably associated with the recovery of the normal myogenic capacity. We also found that Cr activates AMPK and induces an upregulation of PGC-1α expression, two events which are likely to contribute to the protection of mitochondrial quality and function.
Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino, Italy; Interuniversity Institute of Myology (IIM), Urbino, Italy.
Elena
0000-0002-3480-7983
E
Barbieri
Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino, Italy.
Michele
M
Guescini
Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino, Italy; Department for Life Quality Studies, Alma Mater Studiorum, University of Bologna, 47921 Rimini, Italy.
Cinzia
C
Calcabrini
Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino, Italy.
Luciana
L
Vallorani
Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino, Italy.
Anna Rita
AR
Diaz
Department for Life Quality Studies, Alma Mater Studiorum, University of Bologna, 47921 Rimini, Italy.
Carmela
0000-0002-2461-8214
C
Fimognari
Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino, Italy.
Barbara
B
Canonico
Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino, Italy.
Francesca
F
Luchetti
Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino, Italy.
Stefano
S
Papa
Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino, Italy.
Michela
M
Battistelli
Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino, Italy.
Elisabetta
E
Falcieri
Department of Biomedical Sciences, University of Padova, Venetian Institute of Molecular Medicine, 35129 Padova, Italy.
Vanina
V
Romanello
Interuniversity Institute of Myology (IIM), Urbino, Italy; Department of Biomedical Sciences, University of Padova, Venetian Institute of Molecular Medicine, 35129 Padova, Italy.
Marco
M
Sandri
Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino, Italy.
Vilberto
V
Stocchi
Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino, Italy.
Caterina
C
Ciacci
Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino, Italy.
Piero
0000-0001-9412-1660
P
Sestili
D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D003401:Creatine / Q000494:pharmacology*; D019610:Cytoprotection; D004272:DNA, Mitochondrial / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004789:Enzyme Activation; D006609:High Mobility Group Proteins / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000633:toxicity; D015227:Lipid Peroxidation / Q000187:drug effects; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008931:Mitochondria, Muscle / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D024510:Muscle Development / Q000187:drug effects*; D032448:Myoblasts, Skeletal / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D018384:Oxidative Stress / Q000187:drug effects*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000378:metabolism; D040901:Proteomics / Q000379:methods; D015398:Signal Transduction / Q000187:drug effects
D004272:DNA, Mitochondrial; D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; C081930:Tfam protein, mouse; D006861:Hydrogen Peroxide; D055372:AMP-Activated Protein Kinases; D003401:Creatine