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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.


Related in: MedlinePlus

A: schematic representation of the redox signaling pathways that are postulated to lead to adaptive activation of transcription factors and upregulation of the expression of cytoprotective proteins following contractile activity in skeletal muscle. TF, transcription factor. [Redrawn and updated from Jackson and McArdle (35).] B: putative sites at which the redox signaling pathway may be modified in aging leading to a failure of adaptive responses to contractile activity. Excess hydrogen peroxide generated by mitochondria in the muscle during aging may influence the pathway shown in A at multiple points: prevention of activation of NADPH oxidase; a chronic increase in cytosolic hydrogen peroxide; aberrant chronic oxidation of glutathione and other redox sensitive signaling proteins; oxidation of the nuclear environment leading to a failure of TF to activate transcription. AP1, activator protein-1; HSF1, heat shock factor-1; Nrf2, nuclear transcription factor erythroid 2p45-related factor-2.
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Figure 3: A: schematic representation of the redox signaling pathways that are postulated to lead to adaptive activation of transcription factors and upregulation of the expression of cytoprotective proteins following contractile activity in skeletal muscle. TF, transcription factor. [Redrawn and updated from Jackson and McArdle (35).] B: putative sites at which the redox signaling pathway may be modified in aging leading to a failure of adaptive responses to contractile activity. Excess hydrogen peroxide generated by mitochondria in the muscle during aging may influence the pathway shown in A at multiple points: prevention of activation of NADPH oxidase; a chronic increase in cytosolic hydrogen peroxide; aberrant chronic oxidation of glutathione and other redox sensitive signaling proteins; oxidation of the nuclear environment leading to a failure of TF to activate transcription. AP1, activator protein-1; HSF1, heat shock factor-1; Nrf2, nuclear transcription factor erythroid 2p45-related factor-2.

Mentions: Although excess ROS can be deleterious to cells, causing oxidative damage to lipids, DNA and proteins (27), these species also appear to act as mediators of some adaptive processes following cellular stresses under normal physiological conditions. ROS mediate regulatory functions that lead to changes in cell and tissue homeostasis through modification of gene expression (17, 28, 36). Modification of specific thiol residues in proteins appears to be the major mechanism by which ROS exert such regulatory roles (40). Contractile activity increases the intracellular generation of superoxide and NO, and these species plus a number of secondary ROS and RNS (66, 73, 75) can mediate activation of a number of redox-regulated signaling pathways. The nature of these pathways has been the subject of extensive research, and redox-regulated processes (such as activation of NF-κB) have been shown to stimulate the expression of genes associated with myogenesis (2), catabolism, and mitochondrial biogenesis (4, 71, 87). Our group has been particularly interested in the role of ROS in activation of short-term cytoprotective changes in expression of regulatory enzymes and cytoprotective proteins in response to contractile activity (30, 53, 54). This appears to occur through redox-dependent activation of a number of transcriptional pathways, including the transcription factors, NF-κB, activator protein-1, heat shock factor-1 and nuclear transcription factor erythroid 2p45-related factor-2 (36, 42, 77, 91); see Fig. 3A.


Redox regulation of muscle adaptations to contractile activity and aging.

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

A: schematic representation of the redox signaling pathways that are postulated to lead to adaptive activation of transcription factors and upregulation of the expression of cytoprotective proteins following contractile activity in skeletal muscle. TF, transcription factor. [Redrawn and updated from Jackson and McArdle (35).] B: putative sites at which the redox signaling pathway may be modified in aging leading to a failure of adaptive responses to contractile activity. Excess hydrogen peroxide generated by mitochondria in the muscle during aging may influence the pathway shown in A at multiple points: prevention of activation of NADPH oxidase; a chronic increase in cytosolic hydrogen peroxide; aberrant chronic oxidation of glutathione and other redox sensitive signaling proteins; oxidation of the nuclear environment leading to a failure of TF to activate transcription. AP1, activator protein-1; HSF1, heat shock factor-1; Nrf2, nuclear transcription factor erythroid 2p45-related factor-2.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4526708&req=5

Figure 3: A: schematic representation of the redox signaling pathways that are postulated to lead to adaptive activation of transcription factors and upregulation of the expression of cytoprotective proteins following contractile activity in skeletal muscle. TF, transcription factor. [Redrawn and updated from Jackson and McArdle (35).] B: putative sites at which the redox signaling pathway may be modified in aging leading to a failure of adaptive responses to contractile activity. Excess hydrogen peroxide generated by mitochondria in the muscle during aging may influence the pathway shown in A at multiple points: prevention of activation of NADPH oxidase; a chronic increase in cytosolic hydrogen peroxide; aberrant chronic oxidation of glutathione and other redox sensitive signaling proteins; oxidation of the nuclear environment leading to a failure of TF to activate transcription. AP1, activator protein-1; HSF1, heat shock factor-1; Nrf2, nuclear transcription factor erythroid 2p45-related factor-2.
Mentions: Although excess ROS can be deleterious to cells, causing oxidative damage to lipids, DNA and proteins (27), these species also appear to act as mediators of some adaptive processes following cellular stresses under normal physiological conditions. ROS mediate regulatory functions that lead to changes in cell and tissue homeostasis through modification of gene expression (17, 28, 36). Modification of specific thiol residues in proteins appears to be the major mechanism by which ROS exert such regulatory roles (40). Contractile activity increases the intracellular generation of superoxide and NO, and these species plus a number of secondary ROS and RNS (66, 73, 75) can mediate activation of a number of redox-regulated signaling pathways. The nature of these pathways has been the subject of extensive research, and redox-regulated processes (such as activation of NF-κB) have been shown to stimulate the expression of genes associated with myogenesis (2), catabolism, and mitochondrial biogenesis (4, 71, 87). Our group has been particularly interested in the role of ROS in activation of short-term cytoprotective changes in expression of regulatory enzymes and cytoprotective proteins in response to contractile activity (30, 53, 54). This appears to occur through redox-dependent activation of a number of transcriptional pathways, including the transcription factors, NF-κB, activator protein-1, heat shock factor-1 and nuclear transcription factor erythroid 2p45-related factor-2 (36, 42, 77, 91); see Fig. 3A.

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