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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.


Blood hematocrit (%) and rhEPO dosage over the 8 week treatment period. Data are means ± SEM. Asterisk * indicates significant difference pre vs. post, p < 0.05.
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Figure 1: Blood hematocrit (%) and rhEPO dosage over the 8 week treatment period. Data are means ± SEM. Asterisk * indicates significant difference pre vs. post, p < 0.05.

Mentions: The rhEpo treatment aimed to increase the hematocrit (Hct) to ∼50% and to maintain that value throughout the study period. The value of 50% was chosen, partly from a health perspective to minimize the risk of thrombosis and partly because it is the maximum allowed value in many sports. We treated the subjects with the following regime: 1 week of daily sub-cutaneous (SC) injections of 5000 IU of rhEpo (NeoRecormon Roche, Schweiz), followed by 1 week without treatment. Thereafter the subjects were given one weekly SC injection for 7 weeks, titrating the rhEpo dosage (Figure 1) depending on their Hct level (giving either 0, 2500, or 5000 IU). The subjects were instructed to take daily iron supplements of 100 mg throughout the study period, starting 2 weeks prior to the rhEpo treatment. Venous blood was drawn to assess blood hematocrit (Radiometer, ABL 800, Denmark) weekly to monitor the Hct value over the course of rhEpo treatment.


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)

Blood hematocrit (%) and rhEPO dosage over the 8 week treatment period. 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 1: Blood hematocrit (%) and rhEPO dosage over the 8 week treatment period. Data are means ± SEM. Asterisk * indicates significant difference pre vs. post, p < 0.05.
Mentions: The rhEpo treatment aimed to increase the hematocrit (Hct) to ∼50% and to maintain that value throughout the study period. The value of 50% was chosen, partly from a health perspective to minimize the risk of thrombosis and partly because it is the maximum allowed value in many sports. We treated the subjects with the following regime: 1 week of daily sub-cutaneous (SC) injections of 5000 IU of rhEpo (NeoRecormon Roche, Schweiz), followed by 1 week without treatment. Thereafter the subjects were given one weekly SC injection for 7 weeks, titrating the rhEpo dosage (Figure 1) depending on their Hct level (giving either 0, 2500, or 5000 IU). The subjects were instructed to take daily iron supplements of 100 mg throughout the study period, starting 2 weeks prior to the rhEpo treatment. Venous blood was drawn to assess blood hematocrit (Radiometer, ABL 800, Denmark) weekly to monitor the Hct value over the course of rhEpo treatment.

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.