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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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A: force-frequency relationship for mouse extensor digitorum longus muscles. B: reduction of cytochrome c in microdialysates from gastrocnemius muscle of control mice. Muscles were stimulated to contract at 60–75 min (Stimulation) with a protocol of electrical stimuli at 100 Hz (solid bars) or 59 Hz (open bars). Values are means ± SE (n = 4). *P < 0.05 vs. values obtained immediately before contractile activity (45–60 min). #P < 0.05 vs. values obtained immediately before contractile activity (45–60 min). No differences were seen between reduction in cytochrome c with the two different stimulation protocols. NS, not significant.
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Figure 3: A: force-frequency relationship for mouse extensor digitorum longus muscles. B: reduction of cytochrome c in microdialysates from gastrocnemius muscle of control mice. Muscles were stimulated to contract at 60–75 min (Stimulation) with a protocol of electrical stimuli at 100 Hz (solid bars) or 59 Hz (open bars). Values are means ± SE (n = 4). *P < 0.05 vs. values obtained immediately before contractile activity (45–60 min). #P < 0.05 vs. values obtained immediately before contractile activity (45–60 min). No differences were seen between reduction in cytochrome c with the two different stimulation protocols. NS, not significant.

Mentions: The data presented in Fig. 1 and Table 1 show that exposure of muscle to oxypurinol induced a significant depression in maximum tetanic force generation by EDL and soleus muscles and a reduction in contraction-induced extracellular superoxide anion. It appeared feasible that the effect of oxypurinol to reduce muscle force generation may have been responsible for the reduced superoxide release, rather than any direct effect of oxypurinol on XO activity reducing superoxide release. To examine this possibility, we examined the force-frequency curve for untreated EDL muscles (Fig. 3A) and calculated the stimulation frequency required to produce a force equivalent to that seen in the oxypurinol-treated muscles. A reduction in stimulation frequency to 59 Hz was calculated to generate force equivalent to that achieved at 100 Hz in muscles from oxypurinol-treated mice. The data in Fig. 3B show that the increase in extracellular superoxide anion was unaffected by the frequency of stimulation and, hence, force generation.


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)

A: force-frequency relationship for mouse extensor digitorum longus muscles. B: reduction of cytochrome c in microdialysates from gastrocnemius muscle of control mice. Muscles were stimulated to contract at 60–75 min (Stimulation) with a protocol of electrical stimuli at 100 Hz (solid bars) or 59 Hz (open bars). Values are means ± SE (n = 4). *P < 0.05 vs. values obtained immediately before contractile activity (45–60 min). #P < 0.05 vs. values obtained immediately before contractile activity (45–60 min). No differences were seen between reduction in cytochrome c with the two different stimulation protocols. NS, not significant.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: A: force-frequency relationship for mouse extensor digitorum longus muscles. B: reduction of cytochrome c in microdialysates from gastrocnemius muscle of control mice. Muscles were stimulated to contract at 60–75 min (Stimulation) with a protocol of electrical stimuli at 100 Hz (solid bars) or 59 Hz (open bars). Values are means ± SE (n = 4). *P < 0.05 vs. values obtained immediately before contractile activity (45–60 min). #P < 0.05 vs. values obtained immediately before contractile activity (45–60 min). No differences were seen between reduction in cytochrome c with the two different stimulation protocols. NS, not significant.
Mentions: The data presented in Fig. 1 and Table 1 show that exposure of muscle to oxypurinol induced a significant depression in maximum tetanic force generation by EDL and soleus muscles and a reduction in contraction-induced extracellular superoxide anion. It appeared feasible that the effect of oxypurinol to reduce muscle force generation may have been responsible for the reduced superoxide release, rather than any direct effect of oxypurinol on XO activity reducing superoxide release. To examine this possibility, we examined the force-frequency curve for untreated EDL muscles (Fig. 3A) and calculated the stimulation frequency required to produce a force equivalent to that seen in the oxypurinol-treated muscles. A reduction in stimulation frequency to 59 Hz was calculated to generate force equivalent to that achieved at 100 Hz in muscles from oxypurinol-treated mice. The data in Fig. 3B show that the increase in extracellular superoxide anion was unaffected by the frequency of stimulation and, hence, force generation.

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