GSK-3β negatively regulates skeletal myotube hypertrophy

Vyas, Dharmesh; Spangenburg, Espen E.; Abraha, Tsghe W.; Childs, Thomas E.; Booth, Frank W.

doi:10.1152/ajpcell.00049.2002

Cited by 138 publications

(134 citation statements)

References 15 publications

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“…With LiCl alone, myotubes were also larger than both 3% serum-and insulin-treated cells ( Figure 5A, LiCl). These results are consistent with reports showing that insulin alone (Rommel et al, 2001) or LiCl alone (Vyas et al, 2002) can increase myotube size and thus stimulate hypertrophy. However, when insulin and LiCl were used together, the resulting myotubes were considerably larger (ϳ5-fold greater than 3% serum-and 3-fold than insulin-treated cells) ( Figure 5A, insulinϩLiCl).…”

Section: Inhibition Of Gsk-3 By Lithium Chloride Cooperates With Insusupporting

confidence: 93%

“…Here, we focused on the serine/threonine kinase GSK-3, a major substrate phosphorylated and down-regulated by PKB/Akt in a number of cellular systems (Cross et al, 1995). Its inhibition via the PI3K-PKB/Akt signaling cascade has recently been shown to play an important role in IGF-induced myotube hypertrophy (Rommel et al, 2001;Vyas et al, 2002;Pallafacchina et al, 2002) and in overloaded skeletal muscle . We show here that GSK-3 activity is down-regulated in differentiating myotubes because the basal phosphorylation of GSK-3 increases between proliferative C2.7 myoblasts and differentiated myotubes but not in reserve cells, further supporting that GSK-3 inhibition plays an integral role in the process of muscle differentiation.…”

Section: Discussionmentioning

confidence: 99%

“…GSK-3 inhibition has an established role in neuronal plasticity and against apoptosis (Grimes and Jope, 2001). In addition, it has been implicated in IGF-induced myotube hypertrophy by regulating the translation factor eukaryotic initiation factor 2B (eIF2B) and by consequence the level of protein synthesis in myotubes (Rommel et al, 2001;Vyas et al, 2002). Further evidence for a role of GSK-3 in muscle differentiation is its implication as a component in Wnt signaling during embryogenesis.…”

Section: Introductionmentioning

confidence: 99%

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Insulin and Wnt1 Pathways Cooperate to Induce Reserve Cell Activation in Differentiation and Myotube Hypertrophy

Rochat

Fernandez

Vandromme

et al. 2004

MBoC

129

113

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During ex vivo myoblast differentiation, a pool of quiescent mononucleated myoblasts, reserve cells, arise alongside myotubes. Insulin/insulin-like growth factor (IGF) and PKB/Akt-dependent phosphorylation activates skeletal muscle differentiation and hypertrophy. We have investigated the role of glycogen synthase kinase 3 (GSK-3) inhibition by protein kinase B (PKB)/Akt and Wnt/␤-catenin pathways in reserve cell activation during myoblast differentiation and myotube hypertrophy. Inhibition of GSK-3 by LiCl or SB216763, restored insulin-dependent differentiation of C2ind myoblasts in low serum, and cooperated with insulin in serum-free medium to induce MyoD and myogenin expression in C2ind myoblasts, quiescent C2 or primary human reserve cells. We show that LiCl treatment induced nuclear accumulation of ␤-catenin in C2 myoblasts, thus mimicking activation of canonical Wnt signaling. Similarly to the effect of GSK-3 inhibitors with insulin, coculturing C2 reserve cells with Wnt1-expressing fibroblasts enhanced insulinstimulated induction of MyoD and myogenin in reserve cells. A similar cooperative effect of LiCl or Wnt1 with insulin was observed during late ex vivo differentiation and promoted increased size and fusion of myotubes. We show that this synergistic effect on myotube hypertrophy involved an increased fusion of reserve cells into preexisting myotubes. These data reveal insulin and Wnt/␤-catenin pathways cooperate in muscle cell differentiation through activation and recruitment of satellite cell-like reserve myoblasts. INTRODUCTIONSatellite cells are skeletal muscle adult stem cells that participate in postnatal muscle growth and regeneration. Although satellite cells are normally quiescent in adult muscle, they are responsible for muscle regeneration after injury and involved in work-or load-induced muscle fiber hypertrophy (Rosenblatt and Parry, 1992;Schultz and McCormick, 1994;De Angelis et al., 1999;Semsarian et al., 1999;Bodine et al., 2001).Ex vivo models such as myogenic cell lines were isolated from adult mouse muscle and as such are derived from adult satellite cells. At the proliferative stage, myoblasts (activated satellite cells) can be grown extensively in high serum-containing medium and express MyoD, a musclespecific transcription factor that regulates the differentiation process (Weintraub, 1993). When serum levels are lowered, myoblasts exit the cell cycle and spontaneously differentiate, giving rise to a heterogeneous population of cells. The first and major subpopulation is composed of myotubes, quiescent multinucleated cells expressing muscle-specific structural proteins. The remaining subset is composed of quiescent, mononucleated and undifferentiated cells termed reserve cells. Reserve cells retain the ability to be activated and proliferate after which they can be induced to differentiate, leading again to a new mixed population of myotubes and reserve cells. They also express at least two genes characteristic of skeletal muscle stem cells, namely, myf-5 and cd34 and from these c...

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Section: Inhibition Of Gsk-3 By Lithium Chloride Cooperates With Insusupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Insulin and Wnt1 Pathways Cooperate to Induce Reserve Cell Activation in Differentiation and Myotube Hypertrophy

Rochat

Fernandez

Vandromme

et al. 2004

MBoC

129

113

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“…The inhibition of GSK3b by phosphorylation, leads to dephosphorylation activation of glycogen synthase, resulting in glycogen synthesis, and to activation of eIF-2B, which promotes protein synthesis (Rommel et al, 2001). A primary effect of GSK3b inhibition on muscle is the promotion of hypertrophy (Rommel et al, 2001;Vyas et al, 2002). Clearly, with its wide range of targets, GSK3b can mediate a host of other effects.…”

Section: Fibre Size: Mediators Of Muscle Hypertrophy/atrophymentioning

confidence: 99%

Key signalling factors and pathways in the molecular determination of skeletal muscle phenotype

Chang

2007

Animal

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The molecular basis and control of the biochemical and biophysical properties of skeletal muscle, regarded as muscle phenotype, are examined in terms of fibre number, fibre size and fibre types. A host of external factors or stimuli, such as ligand binding and contractile activity, are transduced in muscle into signalling pathways that lead to protein modifications and changes in gene expression which ultimately result in the establishment of the specified phenotype. In skeletal muscle, the key signalling cascades include the Ras-extracellular signal regulated kinase-mitogen activated protein kinase (Erk-MAPK), the phosphatidylinositol 3 0 -kinase (PI3K)-Akt1, p38 MAPK, and calcineurin pathways. The molecular effects of external factors on these pathways revealed complex interactions and functional overlap. A major challenge in the manipulation of muscle of farm animals lies in the identification of regulatory and target genes that could effect defined and desirable changes in muscle quality and quantity. To this end, recent advances in functional genomics that involve the use of micro-array technology and proteomics are increasingly breaking new ground in furthering our understanding of the molecular determinants of muscle phenotype.

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“…GSK-3β is thought to negatively regulate striated muscle hypertrophy (23,40,41). Several studies have suggested that hypertrophic stimuli inhibit the activity of GSK-3β protein by inducing its phosphorylation (23,(40)(41)(42).…”

Section: Discussionmentioning

confidence: 99%

PGF2α-associated vascular smooth muscle hypertrophy is ROS dependent and involves the activation of mTOR, p70S6k, and PTEN

Rice

Uddemarri

Desai

et al. 2008

Prostaglandins & Other Lipid Mediators

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Prostaglandin F 2α (PGF2α) increases reactive oxygen species (ROS) and induces vascular smooth muscle cell (VSMC) hypertrophy by largely unknown mechanism(s). To investigate the signaling events governing PGF2α -induced VSMC hypertrophy we examined the ability of the PGF2α analog, fluprostenol to elicit phosphorylation of Akt, the mammalian target of rapamycin (mTOR), ribosomal protein S6 kinase (p70 S6k ), glycogen synthase kinase-3β (GSK-3β), phosphatase and tensin homolog (PTEN), extracellular signal-regulated kinase 1/2 (ERK1/2) and Jun N-terminal kinase (JNK) in growth arrested A7r5 VSMC. Fluprostenol-induced hypertrophy was associated with increased ROS, mTOR translocation from the nucleus to the cytoplasm, along with Akt, mTOR, GSK-3β, PTEN and ERK1/2 but not JNK phosphorylation. Whereas inhibition of phosphatidylinositol 3-kinase (PI3K) by LY294002 blocked fluprostenol-induced changes in total protein content, pretreatment with rapamycin or with the ERK1/2-MAPK inhibitor UO126 did not. Taken together, these findings suggest that fluprostenol-induced changes in A7R5 hypertrophy involve mTOR translocation and occur through PI3K-dependent mechanisms.

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GSK-3β negatively regulates skeletal myotube hypertrophy

Cited by 138 publications

References 15 publications

Insulin and Wnt1 Pathways Cooperate to Induce Reserve Cell Activation in Differentiation and Myotube Hypertrophy

Insulin and Wnt1 Pathways Cooperate to Induce Reserve Cell Activation in Differentiation and Myotube Hypertrophy

Key signalling factors and pathways in the molecular determination of skeletal muscle phenotype

PGF2α-associated vascular smooth muscle hypertrophy is ROS dependent and involves the activation of mTOR, p70S6k, and PTEN

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