Molecular profiles of Quadriceps muscle in myostatin-null mice reveal PI3K and apoptotic pathways as myostatin targets

Chelh, Ilham; Meunier, Bruno; Picard, Brigitte; Reecy, M James; Chevalier, Catherine; Hocquette, Jean-François; Cassar-Malek, Isabelle

doi:10.1186/1471-2164-10-196

Cited by 72 publications

(62 citation statements)

References 67 publications

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“…Signatures related to muscle energy metabolism and growth As expected (Bouley et al, 2005;Cassar-Malek et al, 2007;Chelh et al, 2009b), our results revealed additional evidences of glycolytic shift within skeletal muscle in the absence of functional MSTN with increased abundance of fast-twitch proteins (e.g. H-MyBP and PGM1) and decreased abundance of H-FABP in DM muscles.…”

Section: Discussionsupporting

confidence: 78%

“…In an earlier study, comparing molecular profiles in the muscles of MSTN-null mice v. their controls, we found differential expression of many genes and proteins related to muscle energy metabolism, activation of the PI3K/Akt signalling pathway and cell survival/apoptosis pathway (Chelh et al, 2009b). In this study, we examined some components of these pathways in the muscles of DM foetuses and DM cows harbouring MSTN loss-of-function.…”

Section: Discussionmentioning

confidence: 88%

“…In the absence of functional MSTN, we showed a differential expression of genes and proteins related to the muscle energy metabolism (Bouley et al, 2005;Cassar-Malek et al, 2007), extracellular-matrix (Cassar-Malek et al, 2007, and cell survival/anti-apoptotic pathway (Cassar-Malek et al, 2007;Chelh et al, 2009b). Activation of the PI3K/Akt pathway (Chelh et al, 2009b) and of anti-apoptotic processes (Chelh et al, 2009a) represents new potential mechanisms to account for muscle hypertrophy as these processes are crucial determinants for muscle protein biosynthesis.…”

Section: Introductionmentioning

confidence: 91%

“…Six genes were selected from the data obtained in MSTNnull mice (Chelh et al, 2009b). The abundance of transcripts was measured by quantitative RT-PCR (qPCR) using SYBR Green I dye.…”

Section: Muscle Samplesmentioning

confidence: 99%

“…Recently, we have examined the molecular profiles in the muscles of DM cattle (Bouley et al, 2005;Cassar-Malek et al, 2007) and of MSTN-null mice (Chelh et al, 2009b) v. their controls. In the absence of functional MSTN, we showed a differential expression of genes and proteins related to the muscle energy metabolism (Bouley et al, 2005;Cassar-Malek et al, 2007), extracellular-matrix (Cassar-Malek et al, 2007, and cell survival/anti-apoptotic pathway (Cassar-Malek et al, 2007;Chelh et al, 2009b).…”

Section: Introductionmentioning

confidence: 99%

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Myostatin inactivation induces a similar muscle molecular signature in double-muscled cattle as in mice

Chelh

Picard

Hocquette

et al. 2011

Animal

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Myostatin (MSTN), a member of the TGF-b superfamily, is a negative regulator of skeletal muscle mass. We have previously shown that the cell survival/apoptosis pathway is a downstream target of MSTN loss-of-function in mice through the regulation of the expression or abundance of many survival and apoptotic factors. In this study, we used western-blot and quantitative PCR (qPCR) analyses to validate these novel downstream targets of MSTN in double-muscled (DM) cattle v. their controls including 260-day-old foetuses and adult cows from the INRA95 strain. MSTN loss-of-function in DM foetuses and DM cows resulted in a glycolytic shift of the muscles (e.g. upregulation of H-MyBP, PGM1 and SNTA1 and downregulation of H-FABP), activation of cell survival pathway through regulation of some components of the PI3K/Akt pathway (e.g. upregulation of DJ-1 and Gsk-3bser9/ Gsk-3btotal ratio and downregulation of PTEN) and upregulation of cell survival factors translationally controlled tumour protein (14-3-3E, Pink1). We also found a lower abundance of pro-apoptotic transcripts and/or proteins (Caspase-3, caspase-8, caspase-9, BID, ID2 and Daxx) and a higher expression of anti-apoptotic transcripts (Traf2 and Bcl2l2) in DM muscles. All together, these results are in favour of activation of the cell survival pathway and loss of apoptosis pathway within the muscles of DM animals. Alteration of both pathways may increase myonuclear or satellite cell survival, which is crucial for protein synthesis. This could contribute to muscle hypertrophy in DM foetuses and DM cows.Keywords: myostatin, cattle, muscle hypertrophy, apoptosis, cell survival ImplicationsMuscle hypertrophy has been extensively studied in meatproducing animals. In double-muscled (DM) cattle, a loss-offunction mutation in the myostatin gene (MSTN ) is responsible for muscle hypertrophy. In order to get a thorough knowledge of the molecular mechanisms of MSTN action, we have examined the molecular phenotype of DM muscle based on our previous data in MSTN-null mice. The data bring new elements to the understanding of the DM muscle phenotype and of the regulation of muscle mass in farm animals.

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Section: Discussionsupporting

confidence: 78%

Section: Discussionmentioning

confidence: 88%

Section: Introductionmentioning

confidence: 91%

“…Six genes were selected from the data obtained in MSTNnull mice (Chelh et al, 2009b). The abundance of transcripts was measured by quantitative RT-PCR (qPCR) using SYBR Green I dye.…”

Section: Muscle Samplesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Myostatin inactivation induces a similar muscle molecular signature in double-muscled cattle as in mice

Chelh

Picard

Hocquette

et al. 2011

Animal

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Characterization and Regulation of Mechanical Loading‐Induced Compensatory Muscle Hypertrophy

Adams

Bamman

2012

Comprehensive Physiology

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In mammalian systems, skeletal muscle exists in a dynamic state that monitors and regulates the physiological investment in muscle size to meet the current level of functional demand. This review attempts to consolidate current knowledge concerning development of the compensatory hypertrophy that occurs in response to a sustained increase in the mechanical loading of skeletal muscle. Topics covered include: defining and measuring compensatory hypertrophy, experimental models, loading stimulus parameters, acute responses to increased loading, hyperplasia, myofiber-type adaptations, the involvement of satellite cells, mRNA translational control, mechanotransduction, and endocrinology. The authors conclude with their impressions of current knowledge gaps in the field that are ripe for future study.

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Insulin‐Like Growth Factor I Regulation and Its Actions in Skeletal Muscle

Vassilakos

Barton

2018

Comprehensive Physiology

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The insulin‐like growth factor (IGF) pathway is essential for promoting growth and survival of virtually all tissues. It bears high homology to its related protein insulin, and as such, there is an interplay between these molecules with regard to their anabolic and metabolic functions. Skeletal muscle produces a significant proportion of IGF‐1, and is highly responsive to its actions, including increased muscle mass and improved regenerative capacity. In this overview, the regulation of IGF‐1 production, stability, and activity in skeletal muscle will be described. Second, the physiological significance of the forms of IGF‐1 produced will be discussed. Last, the interaction of IGF‐1 with other pathways will be addressed. © 2019 American Physiological Society. Compr Physiol 9:413‐438, 2019.

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Molecular profiles of Quadriceps muscle in myostatin-null mice reveal PI3K and apoptotic pathways as myostatin targets

Cited by 72 publications

References 67 publications

Myostatin inactivation induces a similar muscle molecular signature in double-muscled cattle as in mice

Myostatin inactivation induces a similar muscle molecular signature in double-muscled cattle as in mice

Characterization and Regulation of Mechanical Loading‐Induced Compensatory Muscle Hypertrophy

Insulin‐Like Growth Factor I Regulation and Its Actions in Skeletal Muscle

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