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Redox regulation of muscle adaptations to contractile activity and aging.

Jackson MJ - J. Appl. Physiol. (2015)

Bottom Line: Whether such changes in redox signaling reflect primary age-related changes or are secondary to the fundamental mechanisms is unclear.For instance, denervated muscle fibers within muscles from aged rodents or humans appear to generate large amounts of mitochondrial hydrogen peroxide that could influence adjacent innervated fibers.Thus, in this instance, a "secondary" source of reactive oxygen species may be potentially generated as a result of a primary age-related pathology (loss of neurons), but, nevertheless, may contribute to loss of muscle mass and function during aging.

View Article: PubMed Central - PubMed

Affiliation: MRC-Arthritis Research UK Centre for Integrated Research into Musculoskeletal Ageing (CIMA), Department of Musculoskeletal Biology, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, United Kingdom mjj@liverpool.ac.uk.

No MeSH data available.


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Examples of data derived from different approaches to study reactive oxygen species (ROS) generation in muscle or muscle fibers. A: reduction in glutathione content of muscles from wild-type mice in vivo following a 15-min period of isometric contractile activity. *Significant difference vs. quiescent. [Redrawn from Vasilaki et al. (90).] B: increase in interstitial superoxide monitored by microdialysis in the gastrocnemius muscle of mice during a 15-min period of isometric contractile activity. *Significant difference vs. polyethylene glycol (PEG)-superoxide dismutase (SOD). [Redrawn from Close et al. (11).] C: increase in intracellular 2′,7′-dichlorofluorescein (DCF) fluorescence from fibers isolated from the flexor digitorum brevis (FDB) muscle of mice and subjected to 15 min of isometric contractile activity in vitro. *Significant difference vs. baseline. [Redrawn from Palomero et al. (66).] D: increase in hydrogen peroxide content (indicated by increased HyPer fluorescence) in fibers isolated from the FDB muscle of mice and subjected to 10 min of isometric contractile activity in vitro. *Significant difference vs. baseline. [Redrawn from Pearson et al. (69).]
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Figure 1: Examples of data derived from different approaches to study reactive oxygen species (ROS) generation in muscle or muscle fibers. A: reduction in glutathione content of muscles from wild-type mice in vivo following a 15-min period of isometric contractile activity. *Significant difference vs. quiescent. [Redrawn from Vasilaki et al. (90).] B: increase in interstitial superoxide monitored by microdialysis in the gastrocnemius muscle of mice during a 15-min period of isometric contractile activity. *Significant difference vs. polyethylene glycol (PEG)-superoxide dismutase (SOD). [Redrawn from Close et al. (11).] C: increase in intracellular 2′,7′-dichlorofluorescein (DCF) fluorescence from fibers isolated from the flexor digitorum brevis (FDB) muscle of mice and subjected to 15 min of isometric contractile activity in vitro. *Significant difference vs. baseline. [Redrawn from Palomero et al. (66).] D: increase in hydrogen peroxide content (indicated by increased HyPer fluorescence) in fibers isolated from the FDB muscle of mice and subjected to 10 min of isometric contractile activity in vitro. *Significant difference vs. baseline. [Redrawn from Pearson et al. (69).]

Mentions: A number of different approaches have been used to demonstrate the increase in ROS that occurs during contractile activity. Although most data to date have been generated using nonspecific approaches, techniques have become increasingly sophisticated such that (for instance) new specific, genetically encoded fluorescent probes, such as HyPer, can report changes in single species in defined subcellular compartments (see Fig. 1 for examples of approaches that have been used). Much of the initial work in this area was based on the assumption that mitochondria were the main source of the ROS generated during contractile activity in muscle, but several recent publications disagree with this possibility (73). There is some debate about the precise location of NAD(P)H oxidase(s) that has been claimed as an alternative sources, but the presence of this enzyme in the skeletal muscle plasma membrane (41), sarcoplasmic reticulum (97), and the T-tubules (19) has been reported. The T-tubule localized enzyme appears to be particularly relevant, since it has been claimed to be specifically activated by contractions (19). In recent studies, we have examined the potential contribution of mitochondrial and nonmitochondrial sources to the acute increase in superoxide seen during muscle contractions (69, 79) and concluded that NADPH oxidase effects predominated over mitochondria during the short contraction periods (10–15 min) that were studied. Thus present data appear to indicate that a nonmitochondrial NADPH oxidase (likely to be the Nox2 isoform) is the major source of generation of superoxide during short-term contractile activity. The Nox4 isoform of NADPH oxidase has also been reported to be expressed in mitochondria and sarcoplasmic reticulum of skeletal muscle (79, 85), but any role in contraction-induced superoxide generation is unclear.


Redox regulation of muscle adaptations to contractile activity and aging.

Jackson MJ - J. Appl. Physiol. (2015)

Examples of data derived from different approaches to study reactive oxygen species (ROS) generation in muscle or muscle fibers. A: reduction in glutathione content of muscles from wild-type mice in vivo following a 15-min period of isometric contractile activity. *Significant difference vs. quiescent. [Redrawn from Vasilaki et al. (90).] B: increase in interstitial superoxide monitored by microdialysis in the gastrocnemius muscle of mice during a 15-min period of isometric contractile activity. *Significant difference vs. polyethylene glycol (PEG)-superoxide dismutase (SOD). [Redrawn from Close et al. (11).] C: increase in intracellular 2′,7′-dichlorofluorescein (DCF) fluorescence from fibers isolated from the flexor digitorum brevis (FDB) muscle of mice and subjected to 15 min of isometric contractile activity in vitro. *Significant difference vs. baseline. [Redrawn from Palomero et al. (66).] D: increase in hydrogen peroxide content (indicated by increased HyPer fluorescence) in fibers isolated from the FDB muscle of mice and subjected to 10 min of isometric contractile activity in vitro. *Significant difference vs. baseline. [Redrawn from Pearson et al. (69).]
© Copyright Policy - open-access
Related In: Results  -  Collection

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Figure 1: Examples of data derived from different approaches to study reactive oxygen species (ROS) generation in muscle or muscle fibers. A: reduction in glutathione content of muscles from wild-type mice in vivo following a 15-min period of isometric contractile activity. *Significant difference vs. quiescent. [Redrawn from Vasilaki et al. (90).] B: increase in interstitial superoxide monitored by microdialysis in the gastrocnemius muscle of mice during a 15-min period of isometric contractile activity. *Significant difference vs. polyethylene glycol (PEG)-superoxide dismutase (SOD). [Redrawn from Close et al. (11).] C: increase in intracellular 2′,7′-dichlorofluorescein (DCF) fluorescence from fibers isolated from the flexor digitorum brevis (FDB) muscle of mice and subjected to 15 min of isometric contractile activity in vitro. *Significant difference vs. baseline. [Redrawn from Palomero et al. (66).] D: increase in hydrogen peroxide content (indicated by increased HyPer fluorescence) in fibers isolated from the FDB muscle of mice and subjected to 10 min of isometric contractile activity in vitro. *Significant difference vs. baseline. [Redrawn from Pearson et al. (69).]
Mentions: A number of different approaches have been used to demonstrate the increase in ROS that occurs during contractile activity. Although most data to date have been generated using nonspecific approaches, techniques have become increasingly sophisticated such that (for instance) new specific, genetically encoded fluorescent probes, such as HyPer, can report changes in single species in defined subcellular compartments (see Fig. 1 for examples of approaches that have been used). Much of the initial work in this area was based on the assumption that mitochondria were the main source of the ROS generated during contractile activity in muscle, but several recent publications disagree with this possibility (73). There is some debate about the precise location of NAD(P)H oxidase(s) that has been claimed as an alternative sources, but the presence of this enzyme in the skeletal muscle plasma membrane (41), sarcoplasmic reticulum (97), and the T-tubules (19) has been reported. The T-tubule localized enzyme appears to be particularly relevant, since it has been claimed to be specifically activated by contractions (19). In recent studies, we have examined the potential contribution of mitochondrial and nonmitochondrial sources to the acute increase in superoxide seen during muscle contractions (69, 79) and concluded that NADPH oxidase effects predominated over mitochondria during the short contraction periods (10–15 min) that were studied. Thus present data appear to indicate that a nonmitochondrial NADPH oxidase (likely to be the Nox2 isoform) is the major source of generation of superoxide during short-term contractile activity. The Nox4 isoform of NADPH oxidase has also been reported to be expressed in mitochondria and sarcoplasmic reticulum of skeletal muscle (79, 85), but any role in contraction-induced superoxide generation is unclear.

Bottom Line: Whether such changes in redox signaling reflect primary age-related changes or are secondary to the fundamental mechanisms is unclear.For instance, denervated muscle fibers within muscles from aged rodents or humans appear to generate large amounts of mitochondrial hydrogen peroxide that could influence adjacent innervated fibers.Thus, in this instance, a "secondary" source of reactive oxygen species may be potentially generated as a result of a primary age-related pathology (loss of neurons), but, nevertheless, may contribute to loss of muscle mass and function during aging.

View Article: PubMed Central - PubMed

Affiliation: MRC-Arthritis Research UK Centre for Integrated Research into Musculoskeletal Ageing (CIMA), Department of Musculoskeletal Biology, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, United Kingdom mjj@liverpool.ac.uk.

No MeSH data available.


Related in: MedlinePlus