IGF-I does not prevent myotube atrophy caused by proinflammatory cytokines despite activation of Akt/Foxo and GSK-3β pathways and inhibition of atrogin-1 mRNA

Dehoux, Mischaël; Gobier, Catherine; Lause, Pascale; Bertrand, Luc; Ketelslegers, Jean‐Marie; Thissen, Jean‐Paul

doi:10.1152/ajpendo.00085.2006

Cited by 46 publications

(33 citation statements)

References 43 publications

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“…The observations reported here indicating variable ability of IGF to inhibit muscle protein degradation depending on culture conditions is consistent with a number of in vivo reports (18,26,38). IGF-I, even at very high concentrations conferred by strong musclespecific promoters, could not inhibit muscle atrophy and/or protein degradation in response to disuse atrophy (18), sepsis (38), or proinflammatory cytokines (22). In contrast, IGF-I inhibited muscle protein breakdown in response to severe burns (26) and glucocorticoid administration (44,73).…”

Section: Discussionsupporting

confidence: 91%

“…In contrast to the documented effects of IGF on muscle protein synthesis, reports concerning the ability of IGF to inhibit muscle protein degradation are much more variable (22,26,38). In the cell culture system described here, myoblastindependent hypertrophy stimulated by IGF primarily involved stimulation of protein synthesis, rather than inhibition of protein degradation.…”

Section: Discussionmentioning

confidence: 84%

“…In contrast, IGF-I inhibited muscle protein breakdown in response to severe burns (26) and glucocorticoid administration (44,73). Recent studies have suggested the existence of at least two signal pathways leading to muscle proteolysis, only one of which is inhibited by IGF and Akt signaling (22).…”

Section: Discussionmentioning

confidence: 99%

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Muscle-specific overexpression of the type 1 IGF receptor results in myoblast-independent muscle hypertrophy via PI3K, and not calcineurin, signaling

Quinn¹,

Anderson²,

Plymate³

2007

American Journal of Physiology-Endocrinology and Metabolism

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Quinn LS, Anderson BG, Plymate SR. Muscle-specific overexpression of the type 1 IGF receptor results in myoblast-independent muscle hypertrophy via PI3K, and not calcineurin, signaling. Am J Physiol Endocrinol Metab 293: E1538-E1551, 2007. First published October 16, 2007; doi:10.1152/ajpendo.00160.2007.-The insulinlike growth factors (IGF-I and IGF-II), working through the type 1 IGF receptor (IGF-1R), are key mediators of skeletal muscle fiber growth and hypertrophy. These processes are largely dependent on stimulation of proliferation and differentiation of muscle precursor cells, termed myoblasts. It has not been rigorously determined whether the IGFs can also mediate skeletal muscle hypertrophy in a myoblast-independent fashion. Similarly, although the phosphatidylinositol 3-kinase (PI3K) and calcineurin signaling pathways have been implicated in skeletal muscle hypertrophy, these pathways are also involved in skeletal myoblast differentiation. To determine whether the IGFs can stimulate skeletal muscle hypertrophy in a myoblast-independent fashion, we developed and validated a retroviral expression vector that mediated overexpression of the human IGF-1R in rat L6 skeletal myotubes (immature muscle fibers), but not in myoblasts. L6 myotubes transduced with this vector accumulated significantly higher amounts of myofibrillar proteins, in a ligand-and receptor-dependent manner, than controls and demonstrated significantly increased rates of protein synthesis. Stimulation of myotube hypertrophy was independent of myoblast contributions, inasmuch as these cultures did not exhibit increased levels of myoblast proliferation or differentiation. Experiments with PI3K and calcineurin inhibitors indicated that myoblast-independent myotube hypertrophy was mediated by PI3K, but not calcineurin, signaling. This study demonstrates that IGF can mediate skeletal muscle hypertrophy in a myoblast-independent fashion and suggests that muscle-specific overexpression of the IGF-1R or stimulation of its signaling pathways could be used to develop strategies to ameliorate muscle wasting without stimulating proliferative pathways leading to carcinogenesis or other pathological sequelae.insulin-like growth factor; insulin-like growth factor receptor; protein synthesis; protein degradation; sarcopenia THE INSULIN-LIKE GROWTH FACTORS (IGF-I and IGF-II), signaling via the type 1 IGF receptor (IGF-1R) are crucial mediators of skeletal muscle development, hypertrophy, and regeneration (7,29,33,46,60). IGF signaling is required for fetal skeletal muscle development (7,29,46,60), a process largely dependent on the proliferation and differentiation of muscle precursor cells known as myoblasts (5,12,29,51,60). Cell culture studies have shown that the IGFs are strong stimulators of myoblast proliferation and differentiation (15,20,29). Overexpression of the IGF-1R via constitutive promoters in skeletal myogenic cell lines and primary skeletal myogenic cultures also resulted in greatly enhanced proliferation and differentiation responses to I...

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 84%

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Muscle-specific overexpression of the type 1 IGF receptor results in myoblast-independent muscle hypertrophy via PI3K, and not calcineurin, signaling

Quinn¹,

Anderson²,

Plymate³

2007

American Journal of Physiology-Endocrinology and Metabolism

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“…The effect of cytokines on several differentiation markers has already been reported. For example, exposition of differentiated C2C12 myotubes (Di Marco et al 2005) or myoblasts (Dehoux et al 2007) to TNF-α in combination with IFN-γ caused a significant reduction in MHC level with no effect on the fusion index or creatine kinase release. One may expect that prolongation of the present experiment could result in a reduction of MHC in cytokine-treated myogenic cells as a consequence of: i) decreased level of MyoD, a myogenic transcription factor driving the transcription of MHC, ii) activation of proteolytic pathways, mainly the ubiquitin-proteasome system in the presence of cytokines (Langen et al 2004).…”

Section: Discussionmentioning

confidence: 99%

Growth factor and cytokine interactions in myogenesis. Part I. The effect of TNF-α and IFN-γ on IGF-I-dependent differentiation in mouse C2C12 myogenic cells

Wieteska-Skrzeczyńska

Grzelkowska-Kowalczyk²,

Tokarska³

et al. 2011

Polish Journal of Veterinary Sciences

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The aim of this study was to examine the potential interactions of IGF-I with TNF-α and IFN-γ with regard to regulation of the myogenesis and proliferative potential of mouse C2C12 myoblasts. The stimulation of myogenesis by IGF-I (30 nmol/l) was manifested by an enhanced myoblast fusion and expression of myosin heavy chain (MHC) during the first 3 days of differentiation. IGF-I-dependent fusion and MHC expression was reduced by TNF-α and IFN-γ. Both cytokines prevented the stimulatory effect of IGF-I on MyoD expression with minor modification of the myogenin level. Both TNF-α and IFN-γ activated the expression of cyclin A in myoblasts restimulated to proliferation; however, when used in combination with IGF-I these cytokines prevented the rise in cyclin A induced by growth factor. In conclusion: i) TNF-α and IFN-γ reduce IGF-I-dependent myogenesis which was manifested by the reduction of myoblast fusion and MHC cellular levels, ii) Molecular mechanisms of inhibitory action of TNF-α and IFN-γ on IGF-I-mediated differentiation involve a decrease in MyoD whereas myogenin level plays a minor role, iii) TNF-α and IFN-γ increase the proliferative potential of myoblasts; however, they reduced the mitogenic effect of IGF-I, manifested by a decrease of IGF-I-stimulated cyclin A expression in myoblasts reinduced to proliferation. Interactions among IGF-I and proinflammatory cytokines are therefore important to establish a number of myoblasts and the onset of myogenesis during muscle regeneration.

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“…Chronic systemic inflammation has the potential to inhibit muscle protein synthesis activation. The muscle inflammatory response can attenuate IGF-I activation of mTOR (14,62) and leucine induction of protein synthesis (29). Interestingly, muscle pathways associated with cachexiainduced skeletal muscle wasting also can be activated by mechanical stimuli to produce growth (31,47,49,75).…”

mentioning

confidence: 99%

Lewis lung carcinoma regulation of mechanical stretch-induced protein synthesis in cultured myotubes

Gao

Carson

2016

American Journal of Physiology-Cell Physiology

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IGF-I does not prevent myotube atrophy caused by proinflammatory cytokines despite activation of Akt/Foxo and GSK-3β pathways and inhibition of atrogin-1 mRNA

Abstract: Dehoux M, Gobier C, Lause P, Bertrand L, Ketelslegers J-M, Thissen J-P. IGF-I does not prevent myotube atrophy caused by proinflammatory cytokines despite activation of Akt/Foxo and GSK-3␤ pathways and inhibition of atrogin-1 mRNA.

Cited by 46 publications

References 43 publications

Muscle-specific overexpression of the type 1 IGF receptor results in myoblast-independent muscle hypertrophy via PI3K, and not calcineurin, signaling

Muscle-specific overexpression of the type 1 IGF receptor results in myoblast-independent muscle hypertrophy via PI3K, and not calcineurin, signaling

Growth factor and cytokine interactions in myogenesis. Part I. The effect of TNF-α and IFN-γ on IGF-I-dependent differentiation in mouse C2C12 myogenic cells

Lewis lung carcinoma regulation of mechanical stretch-induced protein synthesis in cultured myotubes

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