A reducing redox environment promotes C2C12 myogenesis: Implications for regeneration in aged muscle

Hansen, Jason M.; Klass, Markus; Harris, Craig; Csete, Marie

doi:10.1016/j.cellbi.2006.11.027

Cited by 94 publications

(89 citation statements)

References 35 publications

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“…S9A (Lower). Insulin-induced ROS was shown to be important for differentiation of myoblasts into myotubes (24)(25)(26). In accordance with these studies, insulin treatment induced Akt2 oxidation and decreased Akt2 activity in myoblasts, unlike the results in myotubes (Fig.…”

Section: Pdgf-induced Oxidation Allows Distinct Regulation Of Akt Kinasesupporting

confidence: 81%

Isoform-specific regulation of Akt by PDGF-induced reactive oxygen species

Wani

Qian

Yin

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

129

115

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Isoform-specific signaling of Akt, a major signaling hub and a prominent therapeutic target, remained poorly defined until recently. Subcellular distribution, tissue-specific expression, substrate specificity, and posttranslational modifications are believed to underlie isoform-specific signaling of Akt. The studies reported here show inhibition of Akt2 activity under physiologically relevant conditions of oxidation created by PDGF-induced reactive oxygen species. Combined MS and functional assays identified Cys124 located in the linker region between the N-terminal pleckstrin homology domain and the catalytic kinase domain as one of the unique regulatory redox sites in Akt2 with functional consequence on PDGF-stimulated glucose uptake. A model is proposed describing the consequence of increased endogenous oxidation induced by extracellular cues such as PDGF on Akt2 activity.disulfide | receptor tyrosine kinase | DCF | DCP-Bio1 P KB/Akt is a major signaling hub between cytokine, growth factor, and integrin signaling pathways of consequence to many biological processes. Energy storage, protein synthesis, cell survival and growth, cell cycle progression, and cell death are differentially regulated by the three known isoforms of Akt kinase: Akt1/PKBα, Akt2/PKBβ, and Akt3/PKBγ (1). Although the molecular features underlying isoform-specific functional predominance are largely unknown, hypotheses to explain Akt isoform specificity include selective interactions with substrates and/ or binding partners, tissue specificity, subcellular location, and temporal changes in activation profiles of Akt isoforms (2). Posttranslational modifications may contribute to this isoform-specific signaling, but reports of modifications are lacking.Reactive oxygen species (ROS) are integral to cytokine and growth factor signaling; ROS generation in response to these extracellular cues is well documented (3). Earlier reports, in particular from Sundaresan et al. (4), showed ROS generation in response to PDGF stimulation of vascular smooth muscle cells and suggested that H 2 O 2 can relay redox signals to regulate physiological signaling in response to growth factors. More recently, it has been shown that PrxI phosphorylation at Y194 by Src family tyrosine kinases inhibited PrxI and resulted in H 2 O 2 accumulation at the cellular membrane where receptor tyrosine kinase activation occurs (5). Unanswered questions include which proteins are oxidized by receptor tyrosine kinase-induced ROS, which specific cysteine site(s) undergo oxidation, and the consequence of oxidation on activity of these proteins and propagation of receptor tyrosine kinase signaling. Recently, the synthesis of several dimedone-based chemoselective reagents capable of specific labeling of sulfenic acid oxidized proteins was reported; these reagents allow for specific enrichment and identification of oxidized proteins (6-10). In this study, we used a biotin-tagged 1,3-cyclohexadione derivative, DCP-Bio1 (Fig. 1A), to investigate isoform-specific effects of PDGF-induced ...

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Section: Pdgf-induced Oxidation Allows Distinct Regulation Of Akt Kinasesupporting

confidence: 81%

Isoform-specific regulation of Akt by PDGF-induced reactive oxygen species

Wani

Qian

Yin

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

129

115

View full text Add to dashboard Cite

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“…A number of studies suggest that the redox state of MPCs is a major determinant of the regenerative capacity of injured skeletal muscle (69)(70)(71)(72)(73)(74) as well as of the proliferation and differentiation of MPCs in vitro (69,73,74). These studies suggest that in an oxidizing milieu MPCs are more responsive to signaling pathways that promote cell differentiation and cell death, whereas in reducing environments MPCs are more responsive to signals that promote cellular proliferation and survival.…”

Section: Discussionmentioning

confidence: 99%

Cytoglobin modulates myogenic progenitor cell viability and muscle regeneration

Singh¹,

Canseco²,

Manda³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Mammalian skeletal muscle can remodel, repair, and regenerate itself by mobilizing satellite cells, a resident population of myogenic progenitor cells. Muscle injury and subsequent activation of myogenic progenitor cells is associated with oxidative stress. Cytoglobin is a hemoprotein expressed in response to oxidative stress in a variety of tissues, including striated muscle. In this study, we demonstrate that cytoglobin is up-regulated in activated myogenic progenitor cells, where it localizes to the nucleus and contributes to cell viability. siRNA-mediated depletion of cytoglobin from C2C12 myoblasts increased levels of reactive oxygen species and apoptotic cell death both at baseline and in response to stress stimuli. Conversely, overexpression of cytoglobin reduced reactive oxygen species levels, caspase activity, and cell death. Mice in which cytoglobin was knocked out specifically in skeletal muscle were generated to examine the role of cytoglobin in vivo. Myogenic progenitor cells isolated from these mice were severely deficient in their ability to form myotubes as compared with myogenic progenitor cells from wild-type littermates. Consistent with this finding, the capacity for muscle regeneration was severely impaired in mice deficient for skeletal-muscle cytoglobin. Collectively, these data demonstrate that cytoglobin serves an important role in muscle repair and regeneration.

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“…However, the possibility cannot be dismissed that other ROS members function as signaling molecules by influencing the redox state in the cells. Interestingly, there have been many contrary reports that ROS generated by TNF-␣ or exogenous H 2 O 2 inhibits muscle differentiation, [43][44][45] and ROS released from the cardiac myocyte are linked to the progression of heart failure. 46 This probably reflects differences in the site of H 2 O 2 production and/or the quantity of H 2 O 2 .…”

Section: Discussionmentioning

confidence: 99%

Endogenous Hydrogen Peroxide Regulates Glutathione Redox via Nuclear Factor Erythroid 2-Related Factor 2 Downstream of Phosphatidylinositol 3-Kinase during Muscle Differentiation

Ding

Choi

Kim

et al. 2008

The American Journal of Pathology

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We reported previously that endogenous reactive oxygen species (ROS) function as myogenic signaling molecules. It has also been determined that excess ROS induce electrophile-response element (EpRE)-driven gene expression via activation of nuclear factor erythroid 2-related factor 2 (Nrf2). Nonetheless, the relationship between the metabolism of ROS (eg, H 2 O 2 ) through glutathione (GSH) up-regulation, GSH-dependent reduction of H 2 O 2 , and Nrf2-dependent gene regulation is not well established. Therefore, we attempted to determine whether H 2 O 2 controls the intracellular GSH redox state via the Nrf2-glutamate-cysteine ligase (GCL)/glutathione reductase (GR)-GSH signaling pathway. In our experiments, enhanced H 2 O 2 generation was accompanied by an increase in both total GSH levels and the GSH/GSSG ratio during muscle differentiation. Both GCL and GR transcriptional expression levels were markedly increased during muscle differentiation but reduced by catalase treatment. Nrf2 protein expression and nuclear translocation increased during myogenesis. The inhibition of GCL, GR, and Nrf2 both by inhibitors and by RNA interference blocked muscle differentiation. Phosphatidylinositol 3-kinase regulated the expression of the GCL C (a catalytic subunit) and GR genes via the induction of Nrf2 nuclear translocation and expression. In conclusion, endogenous H 2 O 2 generated during muscle differentiation not only functions as a signaling molecule, but also regulates the GSH redox state via activation of the Nrf2-GCL/GR-GSH signaling pathway downstream of phosphatidylinositol 3-kinase. (Am J Pathol

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A reducing redox environment promotes C2C12 myogenesis: Implications for regeneration in aged muscle

Cited by 94 publications

References 35 publications

Isoform-specific regulation of Akt by PDGF-induced reactive oxygen species

Isoform-specific regulation of Akt by PDGF-induced reactive oxygen species

Cytoglobin modulates myogenic progenitor cell viability and muscle regeneration

Endogenous Hydrogen Peroxide Regulates Glutathione Redox via Nuclear Factor Erythroid 2-Related Factor 2 Downstream of Phosphatidylinositol 3-Kinase during Muscle Differentiation

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