Mitogen-activated protein kinase signaling is necessary for the maintenance of skeletal muscle mass

Shi, Hao; Scheffler, J. M.; Zeng, Caiyun; Pleitner, Jonathan M.; Hannon, Kevin; Grant, A.L.; Gerrard, D.E.

doi:10.1152/ajpcell.00475.2008

Cited by 87 publications

(77 citation statements)

References 50 publications

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“…In the present study, our results show that cast immobilization of rat hindlimbs decreased the phosphorylation of PKB/Akt and ERK1/2. Our data for ERK1/2 phosphorylation is consistent with that of a previous report, in which an ERK1/2 inhibitor decreased muscle mass and elicited skeletal muscle atrophy 27) . In contrast, the phosphorylation of p38MAPK and SAPK/JNK increased during muscle atrophy.…”

Section: Discussionsupporting

confidence: 92%

“…Another study showed that PKB/Akt activation abolished the induction of atrogin-1 expression in skeletal muscle cells during fasting 3) . The p38 MAPK activation and ERK1/2 inactivation in skeletal muscle atrophy has been shown to be indirectly associated with the expression of MuRF-1 and is regulated by the activation of PKB/ Akt 25,27) . The present study showed that PKB/Akt phosphorylation diminished at day 3 after cast immobilization, but changes in MAPK-isoform phosphorylation were not observed at this time, the morphological changes were manifested from day 7 after cast immobilization.…”

Section: Discussionmentioning

confidence: 99%

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Differential Regulation of MAPK Isoforms during Cast-Immobilization -Induced Atrophy in Rat Gastrocnemius Muscle

Kim

2010

J Phys Ther Sci

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Abstract.[Purpose] The aim of the present study was to determine whether the expression of mitogenactivated protein kinase (MAPK) isoforms is related to cast-immobilization-induced atrophy in rat skeletal muscles.[Subjects] The subjects were 24 male Sprague-Dawley rats aged 7 weeks old.[Methods] The rats were randomly divided into a control group (n=4) and four experimental groups (n=20). The experimental groups were submitted to 3, 7, 14, or 21 days of cast-immobilization to provoke disuse atrophy.[Results] The weights and cross-sectional areas of the cast-immobilized muscles were significantly lower than those of the non-immobilized controls. The PKB/Akt and ERK1/2 phosphorylation in atrophied muscles was significantly lower than those in the non-immobilized controls. However, cast immobilization increased the phosphorylation of p38 MAPK and SAPK/JNK. [Conclusion] These results suggest that cast immobilization-induced atrophy may be mediated by the activation of the ERK1/2, p38 MAPK, and SAPK/ JNK pathways, and that the MAPK isoforms are differently regulated by the PKB/Akt pathway during atrophy in the gastrocnemius muscle.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Differential Regulation of MAPK Isoforms during Cast-Immobilization -Induced Atrophy in Rat Gastrocnemius Muscle

Kim

2010

J Phys Ther Sci

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“…30 In cardiac myocytes, the FAK/cSrc relationship has been implicated as being an upstream mediator of ERK1/2 activity and hypertrophy following cardiomyocyte overload. 31 This relationship must be subject to additional regulatory controls, such as changes in levels of phosphatases, because 56 days following SCI reductions in FAK and cSrc phosphorylation were not associated with altered phosphorylation of ERK1/2, even though it is necessary for growth, maintenance and regulation of muscle myotubes 32 and can be directly related to sarcolemmal tension. 33 Our findings do agree with evidence that ERK1/2 phosphorylation is unchanged following long-term SCI when compared with able-bodied controls.…”

Section: Discussionmentioning

confidence: 99%

Focal adhesion kinase signaling is decreased 56 days following spinal cord injury in rat gastrocnemius

et al. 2015

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Study design: Descriptive study. Objectives: The goal of this study was to determine the effects of spinal cord injury (SCI) on aspects of the focal adhesion kinase (FAK) signaling pathway 56 days post injury in rat gastrocnemius. Setting: This study was conducted in Bronx, NY, USA. Methods: Three-month-old male Wistar rats were exposed to either a sham surgery (n = 10) or complete T4 spinal cord transection (n = 10). Rats were killed 56 days following surgery and the muscle was collected. Following homogenization, proteins of the FAK pathway were analyzed by western immunoblotting or reverse transcription-qPCR. In addition, cellular markers for proteins that target the degradation of FAK were investigated. Results: SCI resulted in significantly lower levels of total and phosphorylated FAK, cSrc and p70S6k, and a trend for increased FRNK protein expression. SCI did not change levels of the α7 or β1 integrin subunits, total or phosphorylated ERK1/2, phosphorylated Akt and TSC2 or total p70S6k. SCI resulted in a greater expression of total Akt. mRNA expression of FAK and the α7 or β1 integrins remained unchanged between sham and SCI groups. Caspase-3/7 activity and Trim72 mRNA and protein expression remained unchanged following SCI. Conclusion: SCI results in diminished FAK signaling and is independent of ERK1/2 and Akt. SCI has no effect on mRNA levels for genes encoding components of the focal adhesion 56 days after injury.

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“…There are several lines of evidence that support this notion. First, when MKP-1, a phosphatase that dephosphorylates and thus inactivate MAPKs, was overexpressed in skeletal muscle fibers, it induced profound muscle fiber atrophy possibly through the ubiquitin-proteasome pathways [44]. This atrophic effect may be conferred through ERK1/2 signaling pathway, yet it does not exclude the possibility of a combined effect of ERK, JNK, and p38 MAPK pathways [44].…”

Section: Mapks and Muscle Atrophymentioning

confidence: 99%

“…First, when MKP-1, a phosphatase that dephosphorylates and thus inactivate MAPKs, was overexpressed in skeletal muscle fibers, it induced profound muscle fiber atrophy possibly through the ubiquitin-proteasome pathways [44]. This atrophic effect may be conferred through ERK1/2 signaling pathway, yet it does not exclude the possibility of a combined effect of ERK, JNK, and p38 MAPK pathways [44]. Second, given the fact that MAPKs play integral roles in innate immunity [45], it is reasonable to speculate that MAPK-mediated cytokine secretion may serve as an indirect effect on skeletal muscle atrophy as seen in chronic inflammation diseases.…”

Section: Mapks and Muscle Atrophymentioning

confidence: 99%

MAPK Pathway in Skeletal Muscle Diseases

Geisler¹,

Shi

Gerrard³

2013

Journal of Veterinary Science and Animal Husbandry

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Mitogen-Activated Protein Kinase (MAPK) pathway is a signal transduction pathway that functions in a wide range of physiological and pathophysiological cellular events including cell proliferation, differentiation, apoptosis, migration, inflammation, metabolic disorders and diseases. In skeletal muscle, it plays an essential role in muscle fiber specialization, muscle mass maintenance, damage induced muscle regeneration and muscle diseases. This review provides an overview of MAPK pathway and its pathophysiological role in skeletal muscle diseases with a primary focus on muscular dystrophy and atrophy.MAPK pathway consists of at least 4 subfamilies that include extracellular signal-regulated kinase 1 and 2 (ERK 1/2), p38α/β/γ/δ MAPK, c-Jun NH2-terminal kinases 1, 2, and 3 (JNK 1/2/3), and ERK5 [1][2][3][4]. MAPKs are a family of protein phosphorylating enzymes [5] that regulate diverse aspects of cellular responses in physiology, immunology, neurobiology, and energy metabolism [6]. Cellular activities regulated by MAPKs include proliferation, differentiation, apoptosis, motility [7,8], stress responses, inflammation, and innate immunity [9][10][11]. MAPK functions through transcriptional activation and posttranslational modification on the downstream substrates. Specifically, MAPKs are involved in the production of antimicrobial factors, cytokines, chemokines, and other inflammatory mediatory factors [12]. In the central nervous system, MAPKs are required for proper neuronal axonal development [13]. MAPKs also play a critical part in energy metabolism through modulating lipid metabolism [14][15][16] and skeletal muscle growth and fiber type [6]. Given the fact that MAPKs play such a fundamental and integral role in a broad range of biological processes, interference of this pathway and their downstream effector proteins may have detrimental consequences leading to either metabolic disorder or diseases. This review mainly focuses on the functional role of MAPK pathway in skeletal muscle diseases. [18,19]. Given the fact that each tier of phosphorylation consists of multiple kinases, one may question how an extracellular signal is decoded and transduced into a specific cellular response in a temporal and spatial manner. The complexity of regulation of the MAPKs provides a platform on which diverse signals converge and are precisely deciphered to generate a specific signal that fine-tunes the signaling network within a cell. On the other hand, an activated MAPK signal has to be curtailed in a timely manner so that cell will not overreact to a stimulus so to maintain metabolic homeostasis. One mechanism involves the dephosphorylation and thus inactivation of MAPKs by the MAPK phosphatases (MKPs) [5]. MKPs, also known as dual-specificity protein phosphatases (DUSPs), are a group of 10 catalytically active protein tyrosine phosphatases [9,20,21]. MKPs inactivate MAPKs through dephosphorylation of MAPKs on regulatory threonine and tyrosine residues. Though the substrates of the MKPs are to some extent overlapp...

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Mitogen-activated protein kinase signaling is necessary for the maintenance of skeletal muscle mass

Cited by 87 publications

References 50 publications

Differential Regulation of MAPK Isoforms during Cast-Immobilization -Induced Atrophy in Rat Gastrocnemius Muscle

Differential Regulation of MAPK Isoforms during Cast-Immobilization -Induced Atrophy in Rat Gastrocnemius Muscle

Focal adhesion kinase signaling is decreased 56 days following spinal cord injury in rat gastrocnemius

MAPK Pathway in Skeletal Muscle Diseases

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