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Erythropoietin treatment enhances muscle mitochondrial capacity in humans.

Plenge U, Belhage B, Guadalupe-Grau A, Andersen PR, Lundby C, Dela F, Stride N, Pott FC, Helge JW, Boushel R - Front Physiol (2012)

Bottom Line: We hypothesized that recombinant human Epo (rhEpo) treatment enhances skeletal muscle mitochondrial oxidative phosphorylation (OXPHOS) capacity in humans.Mitochondrial OXPHOS was quantified by high-resolution respirometry in saponin-permeabilized muscle fibers obtained from biopsies of the vastus lateralis before and after rhEpo treatment.OXPHOS was determined with the mitochondrial complex I substrates malate, glutamate, pyruvate, and complex II substrate succinate in the presence of saturating ADP concentrations, while maximal electron transport capacity (ETS) was assessed by addition of an uncoupler. rhEpo treatment increased OXPHOS (from 92 ± 5 to 113 ± 7 pmol·s(-1)·mg(-1)) and ETS (107 ± 4 to 143 ± 14 pmol·s(-1)·mg(-1), p < 0.05), demonstrating that Epo treatment induces an upregulation of OXPHOS and ETS in human skeletal muscle.

View Article: PubMed Central - PubMed

Affiliation: Department of Anaesthesia, Bispebjerg Hospital Copenhagen, Denmark.

ABSTRACT
Erythropoietin (Epo) treatment has been shown to induce mitochondrial biogenesis in cardiac muscle along with enhanced mitochondrial capacity in mice. We hypothesized that recombinant human Epo (rhEpo) treatment enhances skeletal muscle mitochondrial oxidative phosphorylation (OXPHOS) capacity in humans. In six healthy volunteers rhEpo was administered by sub-cutaneous injection over 8 weeks with oral iron (100 mg) supplementation taken daily. Mitochondrial OXPHOS was quantified by high-resolution respirometry in saponin-permeabilized muscle fibers obtained from biopsies of the vastus lateralis before and after rhEpo treatment. OXPHOS was determined with the mitochondrial complex I substrates malate, glutamate, pyruvate, and complex II substrate succinate in the presence of saturating ADP concentrations, while maximal electron transport capacity (ETS) was assessed by addition of an uncoupler. rhEpo treatment increased OXPHOS (from 92 ± 5 to 113 ± 7 pmol·s(-1)·mg(-1)) and ETS (107 ± 4 to 143 ± 14 pmol·s(-1)·mg(-1), p < 0.05), demonstrating that Epo treatment induces an upregulation of OXPHOS and ETS in human skeletal muscle.

No MeSH data available.


Mitochondrial respiration measured by high-resolution respirometry in permeabilized fibers from the vastus lateralis before and after Epo treatment. OXPHOS; state 3 respiration for Complex I + II before and after rhEpo. ETS; Maximal Electron Transfer System assessed adding FCCP before and after rhEPO treatment. Data are means ± SEM. Asterisk * indicates significant difference pre vs. post, p < 0.05.
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Figure 2: Mitochondrial respiration measured by high-resolution respirometry in permeabilized fibers from the vastus lateralis before and after Epo treatment. OXPHOS; state 3 respiration for Complex I + II before and after rhEpo. ETS; Maximal Electron Transfer System assessed adding FCCP before and after rhEPO treatment. Data are means ± SEM. Asterisk * indicates significant difference pre vs. post, p < 0.05.

Mentions: After Epo treatment state 3 respiration with Complex I substrates (MPG3) was 52 ± 5 before and 64 ± 7 pmol·s−1·mg·1 after rhEpo while respiratory rate for convergent electron supply through the Q-junction for Complex I + II (Figure 2) increased from 92 ± 6 to 113 ± 7 pmol·s−1·mg−1. The substrate control ratio (MPG3/MPGS3) was unchanged (0.56 ± 0.04 vs. 0.56 ± 0.03) by Epo treatment (Table 2), while the maximal ETS measured with FCCP titration increased from 107 ± 4 to 143 ± 13 pmol·s−1·mg−1. The coupling (phosphorylation) control ratio (P/E) reflecting the ratio of OXPHOS to ETS was unchanged (from 0.87 ± 0.04 to 0.83 ± 0.03), indicating similar control of ETS capacity by the OXPHOS system (Table 2). Some of the samples were excluded from statistical analysis due to a high stimulation of respiration by addition of cytochrome c. In the baseline experiments one sample showed an increase of respiration of 26% and in the post Epo experiments 2 samples in different subjects were excluded with responses of 40 and 60% respectively. For these subjects a single respirometric measurement was used in the analysis. The isolated activity of COX was similar before and after (333 ± 25 vs. 320 ± 20 pmol·s−1·mg−1) Epo treatment, as was CS activity (129 ± 10 vs. 139 ± 13 μmol·g−1·min−1, p = 0.06).


Erythropoietin treatment enhances muscle mitochondrial capacity in humans.

Plenge U, Belhage B, Guadalupe-Grau A, Andersen PR, Lundby C, Dela F, Stride N, Pott FC, Helge JW, Boushel R - Front Physiol (2012)

Mitochondrial respiration measured by high-resolution respirometry in permeabilized fibers from the vastus lateralis before and after Epo treatment. OXPHOS; state 3 respiration for Complex I + II before and after rhEpo. ETS; Maximal Electron Transfer System assessed adding FCCP before and after rhEPO treatment. Data are means ± SEM. Asterisk * indicates significant difference pre vs. post, p < 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3299978&req=5

Figure 2: Mitochondrial respiration measured by high-resolution respirometry in permeabilized fibers from the vastus lateralis before and after Epo treatment. OXPHOS; state 3 respiration for Complex I + II before and after rhEpo. ETS; Maximal Electron Transfer System assessed adding FCCP before and after rhEPO treatment. Data are means ± SEM. Asterisk * indicates significant difference pre vs. post, p < 0.05.
Mentions: After Epo treatment state 3 respiration with Complex I substrates (MPG3) was 52 ± 5 before and 64 ± 7 pmol·s−1·mg·1 after rhEpo while respiratory rate for convergent electron supply through the Q-junction for Complex I + II (Figure 2) increased from 92 ± 6 to 113 ± 7 pmol·s−1·mg−1. The substrate control ratio (MPG3/MPGS3) was unchanged (0.56 ± 0.04 vs. 0.56 ± 0.03) by Epo treatment (Table 2), while the maximal ETS measured with FCCP titration increased from 107 ± 4 to 143 ± 13 pmol·s−1·mg−1. The coupling (phosphorylation) control ratio (P/E) reflecting the ratio of OXPHOS to ETS was unchanged (from 0.87 ± 0.04 to 0.83 ± 0.03), indicating similar control of ETS capacity by the OXPHOS system (Table 2). Some of the samples were excluded from statistical analysis due to a high stimulation of respiration by addition of cytochrome c. In the baseline experiments one sample showed an increase of respiration of 26% and in the post Epo experiments 2 samples in different subjects were excluded with responses of 40 and 60% respectively. For these subjects a single respirometric measurement was used in the analysis. The isolated activity of COX was similar before and after (333 ± 25 vs. 320 ± 20 pmol·s−1·mg−1) Epo treatment, as was CS activity (129 ± 10 vs. 139 ± 13 μmol·g−1·min−1, p = 0.06).

Bottom Line: We hypothesized that recombinant human Epo (rhEpo) treatment enhances skeletal muscle mitochondrial oxidative phosphorylation (OXPHOS) capacity in humans.Mitochondrial OXPHOS was quantified by high-resolution respirometry in saponin-permeabilized muscle fibers obtained from biopsies of the vastus lateralis before and after rhEpo treatment.OXPHOS was determined with the mitochondrial complex I substrates malate, glutamate, pyruvate, and complex II substrate succinate in the presence of saturating ADP concentrations, while maximal electron transport capacity (ETS) was assessed by addition of an uncoupler. rhEpo treatment increased OXPHOS (from 92 ± 5 to 113 ± 7 pmol·s(-1)·mg(-1)) and ETS (107 ± 4 to 143 ± 14 pmol·s(-1)·mg(-1), p < 0.05), demonstrating that Epo treatment induces an upregulation of OXPHOS and ETS in human skeletal muscle.

View Article: PubMed Central - PubMed

Affiliation: Department of Anaesthesia, Bispebjerg Hospital Copenhagen, Denmark.

ABSTRACT
Erythropoietin (Epo) treatment has been shown to induce mitochondrial biogenesis in cardiac muscle along with enhanced mitochondrial capacity in mice. We hypothesized that recombinant human Epo (rhEpo) treatment enhances skeletal muscle mitochondrial oxidative phosphorylation (OXPHOS) capacity in humans. In six healthy volunteers rhEpo was administered by sub-cutaneous injection over 8 weeks with oral iron (100 mg) supplementation taken daily. Mitochondrial OXPHOS was quantified by high-resolution respirometry in saponin-permeabilized muscle fibers obtained from biopsies of the vastus lateralis before and after rhEpo treatment. OXPHOS was determined with the mitochondrial complex I substrates malate, glutamate, pyruvate, and complex II substrate succinate in the presence of saturating ADP concentrations, while maximal electron transport capacity (ETS) was assessed by addition of an uncoupler. rhEpo treatment increased OXPHOS (from 92 ± 5 to 113 ± 7 pmol·s(-1)·mg(-1)) and ETS (107 ± 4 to 143 ± 14 pmol·s(-1)·mg(-1), p < 0.05), demonstrating that Epo treatment induces an upregulation of OXPHOS and ETS in human skeletal muscle.

No MeSH data available.