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Effect of xanthine oxidase-generated extracellular superoxide on skeletal muscle force generation.

Gomez-Cabrera MC, Close GL, Kayani A, McArdle A, Viña J, Jackson MJ - Am. J. Physiol. Regul. Integr. Comp. Physiol. (2009)

Bottom Line: Oxypurinol decreased the maximum tetanic force produced by EDL and soleus muscles, and polyethylene glycol-tagged Cu,Zn-SOD decreased the maximum force production by the EDL muscles.Neither agent influenced the rate of decline in force production when EDL or soleus muscles were repeatedly electrically stimulated using a 5-min fatiguing protocol (stimulation at 40 Hz for 0.1 s every 5 s).Thus these studies indicate that XO activity contributes to the increased superoxide anion detected within the extracellular space of skeletal muscles during nondamaging contractile activity and that XO-derived superoxide anion or derivatives of this radical have a positive effect on muscle force generation during isometric contractions of mouse skeletal muscles.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, Faculty of Medicine, University of Valencia, Valencia, Spain.

ABSTRACT
Skeletal muscle contractions increase superoxide anion in skeletal muscle extracellular space. We tested the hypotheses that 1) after an isometric contraction protocol, xanthine oxidase (XO) activity is a source of superoxide anion in the extracellular space of skeletal muscle and 2) the increase in XO-derived extracellular superoxide anion during contractions affects skeletal muscle contractile function. Superoxide anion was monitored in the extracellular space of mouse gastrocnemius muscles by following the reduction of cytochrome c in muscle microdialysates. A 15-min protocol of nondamaging isometric contractions increased the reduction of cytochrome c in microdialysates, indicating an increase in superoxide anion. Mice treated with the XO inhibitor oxypurinol showed a smaller increase in superoxide anions in muscle microdialysates following contractions than in microdialysates from muscles of vehicle-treated mice. Intact extensor digitorum longus (EDL) and soleus muscles from mice were also incubated in vitro with oxypurinol or polyethylene glycol-tagged Cu,Zn-SOD. Oxypurinol decreased the maximum tetanic force produced by EDL and soleus muscles, and polyethylene glycol-tagged Cu,Zn-SOD decreased the maximum force production by the EDL muscles. Neither agent influenced the rate of decline in force production when EDL or soleus muscles were repeatedly electrically stimulated using a 5-min fatiguing protocol (stimulation at 40 Hz for 0.1 s every 5 s). Thus these studies indicate that XO activity contributes to the increased superoxide anion detected within the extracellular space of skeletal muscles during nondamaging contractile activity and that XO-derived superoxide anion or derivatives of this radical have a positive effect on muscle force generation during isometric contractions of mouse skeletal muscles.

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Force production by extensor digitorum longus (A) and soleus (B) muscles incubated in mammalian Ringer solution alone (open symbols, n = 9), oxypurinol (solid symbols, n = 9), and polyethylene glycol-tagged Cu,Zn-SOD (gray symbols, n = 10) during a 5-min fatigue protocol. Values are means ± SE. No significant differences were seen between the different groups of muscles.
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Figure 2: Force production by extensor digitorum longus (A) and soleus (B) muscles incubated in mammalian Ringer solution alone (open symbols, n = 9), oxypurinol (solid symbols, n = 9), and polyethylene glycol-tagged Cu,Zn-SOD (gray symbols, n = 10) during a 5-min fatigue protocol. Values are means ± SE. No significant differences were seen between the different groups of muscles.

Mentions: Figure 2 shows the loss of force generation by EDL and soleus muscles over time during repetitive tetanic contractions at 40 Hz. EDL muscles lost a greater proportion of force over 5 min of repeated stimulations than soleus muscles, but the loss of force generation in EDL or soleus muscles was unaffected by exposure to oxypurinol or PEG-SOD. Similarly, neither agent significantly affected the recovery of force at 2 min following contractions (data not shown in detail).


Effect of xanthine oxidase-generated extracellular superoxide on skeletal muscle force generation.

Gomez-Cabrera MC, Close GL, Kayani A, McArdle A, Viña J, Jackson MJ - Am. J. Physiol. Regul. Integr. Comp. Physiol. (2009)

Force production by extensor digitorum longus (A) and soleus (B) muscles incubated in mammalian Ringer solution alone (open symbols, n = 9), oxypurinol (solid symbols, n = 9), and polyethylene glycol-tagged Cu,Zn-SOD (gray symbols, n = 10) during a 5-min fatigue protocol. Values are means ± SE. No significant differences were seen between the different groups of muscles.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2806206&req=5

Figure 2: Force production by extensor digitorum longus (A) and soleus (B) muscles incubated in mammalian Ringer solution alone (open symbols, n = 9), oxypurinol (solid symbols, n = 9), and polyethylene glycol-tagged Cu,Zn-SOD (gray symbols, n = 10) during a 5-min fatigue protocol. Values are means ± SE. No significant differences were seen between the different groups of muscles.
Mentions: Figure 2 shows the loss of force generation by EDL and soleus muscles over time during repetitive tetanic contractions at 40 Hz. EDL muscles lost a greater proportion of force over 5 min of repeated stimulations than soleus muscles, but the loss of force generation in EDL or soleus muscles was unaffected by exposure to oxypurinol or PEG-SOD. Similarly, neither agent significantly affected the recovery of force at 2 min following contractions (data not shown in detail).

Bottom Line: Oxypurinol decreased the maximum tetanic force produced by EDL and soleus muscles, and polyethylene glycol-tagged Cu,Zn-SOD decreased the maximum force production by the EDL muscles.Neither agent influenced the rate of decline in force production when EDL or soleus muscles were repeatedly electrically stimulated using a 5-min fatiguing protocol (stimulation at 40 Hz for 0.1 s every 5 s).Thus these studies indicate that XO activity contributes to the increased superoxide anion detected within the extracellular space of skeletal muscles during nondamaging contractile activity and that XO-derived superoxide anion or derivatives of this radical have a positive effect on muscle force generation during isometric contractions of mouse skeletal muscles.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, Faculty of Medicine, University of Valencia, Valencia, Spain.

ABSTRACT
Skeletal muscle contractions increase superoxide anion in skeletal muscle extracellular space. We tested the hypotheses that 1) after an isometric contraction protocol, xanthine oxidase (XO) activity is a source of superoxide anion in the extracellular space of skeletal muscle and 2) the increase in XO-derived extracellular superoxide anion during contractions affects skeletal muscle contractile function. Superoxide anion was monitored in the extracellular space of mouse gastrocnemius muscles by following the reduction of cytochrome c in muscle microdialysates. A 15-min protocol of nondamaging isometric contractions increased the reduction of cytochrome c in microdialysates, indicating an increase in superoxide anion. Mice treated with the XO inhibitor oxypurinol showed a smaller increase in superoxide anions in muscle microdialysates following contractions than in microdialysates from muscles of vehicle-treated mice. Intact extensor digitorum longus (EDL) and soleus muscles from mice were also incubated in vitro with oxypurinol or polyethylene glycol-tagged Cu,Zn-SOD. Oxypurinol decreased the maximum tetanic force produced by EDL and soleus muscles, and polyethylene glycol-tagged Cu,Zn-SOD decreased the maximum force production by the EDL muscles. Neither agent influenced the rate of decline in force production when EDL or soleus muscles were repeatedly electrically stimulated using a 5-min fatiguing protocol (stimulation at 40 Hz for 0.1 s every 5 s). Thus these studies indicate that XO activity contributes to the increased superoxide anion detected within the extracellular space of skeletal muscles during nondamaging contractile activity and that XO-derived superoxide anion or derivatives of this radical have a positive effect on muscle force generation during isometric contractions of mouse skeletal muscles.

Show MeSH
Related in: MedlinePlus