Soendergaard 2016 Abstract IOC109
|Soendergaard SD (2016) Acute exposure of human muscle fibers to EPO or Actovegin has a marked effect on the mitochondrial respiratory capacity. Mitochondr Physiol Network 21.01.|
Actovegin, a drug made from the deproteinized hemodialysate of calf blood increases the mitochondrial respiratory capacity of untrained and overweight subjects, indicating that Actovegin may have the potential to improve performance. These findings are interesting because the drug is not on the World Anti-Doping Agency’s prohibited list, but used by athletes. Therefore, we wanted to investigate whether Actovegin had the same effect in trained subjects. Also, we wanted to compare the effect of Actovegin with the effect of erythropoietin (EPO; a banned substance) on the mitochondrial respiratory capacity.
We obtained basal muscle biopsies (m. vastus lateralis) from 8 trained subjects (VO2max: 54±2ml/min/kg). The skeletal muscle fibers were acutely exposed to either Actovegin (50µl/ml) or EPO (50µl/ml, 2000IU) during permeabilization, washing of the fibers and the respiratory analysis, resulting in a ~2h exposure time. Mitochondrial respiratory capacity was measured with high-resolution respirometry (Oxygraph-2k; Oroboros , Innsbruck, Austria) and by sequential addition of malate, glutamate, ADP, succinate and FCCP.
EPO and Actovegin increased maximal complex I activity (P<0.05) compared to control (22±4, 43±3, 61±5pmol/mg/s) with a significant difference between EPO and Actovegin (43±3, 61±5pmol/mg/s, respectively). Only Actovegin increased the maximal oxidative phosphorylation capacity significantly (72±5, 82±8, 95±4pmol/mg/s), but both EPO and Actovegin increased the maximal electron transport system capacity (77±5, 101±9, 112±10pmol/mg/s) (P<0.05). In regards to ADP kinetics, Vmax was significantly increased by EPO and Actovegin (18±2, 33±3, 50±4pmol/mg/s) (P<0.05), whereas Km was unaltered by EPO, but significantly increased by Actovegin (0.18±0.04, 0.21±0.04, 0.72±0.31mM).
The study demonstrates that acute exposure of human muscle fibers to EPO or Actovegin increases the mitochondrial respiratory capacity of trained subjects. The mechanism(s) are not clear, but EPO has been found to increase the NAD+ levels and the NAD+/NADH ratio in myoblasts (1), which could explain the observed increased complex I respiration with EPO (2). Actovegin contains succinate which in part can explain the effect of Actovegin on the mitochondrial respiration. It is not known whether Actovegin also contains NAD+, but it is intriguing to think that Actovegin and EPO might modulate mitochondrial function through the same mechanism, but this is only speculations.
Labels: MiParea: Respiration, Exercise physiology;nutrition;life style, mt-Medicine, Pharmacology;toxicology
Organism: Human Tissue;cell: Skeletal muscle Preparation: Permeabilized tissue
Coupling state: OXPHOS, ET Pathway: N, NS HRR: Oxygraph-2k
Xlab, Center for Healthy Aging, Dept Biomed Sc, Fac Health Sc, Univ Copenhagen, Denmark. - [email protected]
- Wang L, Jia Y, Rogers H, Wu YP, Huang S, Noguchi CT (2016) GATA-binding protein 4 (GATA-4) and T-cell acute leukemia 1 (TAL1) regulate myogenic differentiation and erythropoietin response via cross-talk with Sirtuin1 (Sirt1). J Biol Chem 287:30157-69.
- Hey-Mogensen M, Hojlund K, Vind BF, Wang L, Dela F, Beck-Nielsen H, Fernstrom M, Sahlin K (2010) Effect of physical training on mitochondrial respiration and reactive oxygen species release in skeletal muscle in patients with obesity and type 2 diabetes. Diabetologia 53:1976-85.