Dystrophin glycoprotein complex dysfunction: A regulatory link between muscular dystrophy and cancer cachexia

Acharyya, Swarnali; Butchbach, Matthew E.R.; Sahenk, Zarife; Wang, Huating; Saji, Motoyasu; Carathers, Micheal; Ringel, Matthew D.; Skipworth, Richard J.E.; Fearon, Kenneth C. H.; Hollingsworth, Michael A.; Muscarella, Peter; Burghes, Arthur H.M.; Rafael‐Fortney, Jill A.; Guttridge, Denis C.

doi:10.1016/j.ccr.2005.10.004

Cited by 286 publications

(322 citation statements)

References 58 publications

(81 reference statements)

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“…atrogin1 and MuRF1). Such effects probably also account in part for the ability of IB␣-SR expression to decrease muscle atrophy upon denervation (7) and cancer cachexia (7,37), as well as in fasting (Fig. 2E).…”

Section: Volume 290 • Number 51 • December 18 2015mentioning

confidence: 99%

Muscle Wasting in Fasting Requires Activation of NF-κB and Inhibition of AKT/Mechanistic Target of Rapamycin (mTOR) by the Protein Acetylase, GCN5

Lee

Goldberg

2015

Journal of Biological Chemistry

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NF-B is best known for its pro-inflammatory and anti-apoptotic actions, but in skeletal muscle, NF-B activation is important for atrophy upon denervation or cancer. Here, we show that also upon fasting, NF-B becomes activated in muscle and is critical for the subsequent atrophy. Following food deprivation, the expression and acetylation of the p65 of NF-B on lysine 310 increase markedly in muscles. NF-B inhibition in mouse muscles by overexpression of the IB␣ superrepressor (IB␣-SR) or of p65 mutated at Lys-310 prevented atrophy. Knockdown of GCN5 with shRNA or a dominant-negative GCN5 or overexpression of SIRT1 decreased p65K310 acetylation and muscle wasting upon starvation. In addition to reducing atrogene expression, surprisingly inhibiting NF-B with IB␣-SR or by GCN5 knockdown in these muscles also enhanced AKT and mechanistic target of rapamycin (mTOR) activities, which also contributed to the reduction in atrophy. These new roles of NF-B and GCN5 in regulating muscle proteolysis and AKT/ mTOR signaling suggest novel approaches to combat muscle wasting.

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Section: Volume 290 • Number 51 • December 18 2015mentioning

confidence: 99%

Muscle Wasting in Fasting Requires Activation of NF-κB and Inhibition of AKT/Mechanistic Target of Rapamycin (mTOR) by the Protein Acetylase, GCN5

Lee

Goldberg

2015

Journal of Biological Chemistry

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“…Consistently with this finding, mTOR  muscles display several features reminiscent of mdx and DMD muscles. At the molecular level, these include the up-regulation of utrophin (Tinsley et al, 1998), caveolin-3 (Repetto et al, 1999, and PKB/Akt protein levels (Acharyya et al, 2005;Dogra et al, 2006;Peter and Crosbie, 2006). Finally, the functional characteristics mTOR deficiency leads to severe muscular dystrophy • Risson et al…”

Section: Mtor Deficiency In Muscle Does Not Impair Whole Body Glucosementioning

confidence: 99%

Muscle inactivation of mTOR causes metabolic and dystrophin defects leading to severe myopathy

Risson¹,

Mazelin²,

Roceri³

et al. 2009

J Exp Med

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“…Since laminin is able to stimulate integrin receptors it was unclear whether the molecular mechanisms of AKT inhibition would be accounted by DGC complex or indirectly by the integrin system. A possible solution came from the studies performed by Acharyya et al (2005) on dystrophin expression in cachectic tumor-induced animal models. In atrophic conditions, the authors observed a strong perturbation of the myofibrillar component in skeletal muscle connecting the cachexia tumor-induced with a loss of DGC integrity and the upregulation of muscle wasting became more stressed when the tumors were injected in the mdx animal model, lacking dystrophin expression.…”

Section: Dystrophin-glycoprotein Complex (Dgc)mentioning

confidence: 99%

Cellular mechanisms and local progenitor activation to regulate skeletal muscle mass

Cassano

Quattrocelli

Crippa

et al. 2009

J Muscle Res Cell Motil

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Skeletal muscle hypertrophy is a result of increased load, such as functional and stretch-overload. Activation of satellite cells and proliferation, differentiation and fusion are required for hypertrophy of overloaded skeletal muscles. On the contrary, a dramatic loss of skeletal muscle mass determines atrophy settings. The epigenetic changes involved in gene regulation at DNA and chromatin level are critical for the opposing phenomena, muscle growth and atrophy. Physiological properties of skeletal muscle tissue play a fundamental role in health and disease since it is the most abundant tissue in mammals. In fact, protein synthesis and degradation are finely modulated to maintain an appropriate muscle mass. When the molecular signaling is altered muscle wasting and weakness occurred, and this happened in most common inherited and acquired disorders such as muscular dystrophies, cachexia, and age-related wasting. To date, there is no accepted treatment to improve muscle size and strength, and these conditions pose a considerable anxiety to patients as well as to public health. Several molecules, including Magic-F1, myostatin inhibitor, IGF, glucocorticoids and microRNAs are currently investigated to interfere positively in the blueprint of skeletal muscle growth and regeneration.

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Dystrophin glycoprotein complex dysfunction: A regulatory link between muscular dystrophy and cancer cachexia

Cited by 286 publications

References 58 publications

Muscle Wasting in Fasting Requires Activation of NF-κB and Inhibition of AKT/Mechanistic Target of Rapamycin (mTOR) by the Protein Acetylase, GCN5

Muscle Wasting in Fasting Requires Activation of NF-κB and Inhibition of AKT/Mechanistic Target of Rapamycin (mTOR) by the Protein Acetylase, GCN5

Muscle inactivation of mTOR causes metabolic and dystrophin defects leading to severe myopathy

Cellular mechanisms and local progenitor activation to regulate skeletal muscle mass

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