GSK-3β activity is increased in skeletal muscle after burn injury in rats

Fang, Cheng-Hui; Li, Bing-Guo; James, J. Howard; Yahya, Ayesha; Kadeer, Nijiati; Guo, Xiang; Xiao, Chun; Supp, Dorothy M.; Kagan, Richard J.; Hasselgren, Per-Olof J.; Sheriff, Sulaiman

doi:10.1152/ajpregu.00244.2007

Cited by 24 publications

(27 citation statements)

References 38 publications

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“…For example, inhibition of Akt activity results in reduced phosphorylation (activation) of GSK-3␤. Recent observations support a role of activated GSK-3␤ in muscle wasting caused by sepsis (31) and burn injury (32). Thus, in a recent study (31) we found that muscle levels of phosphorylated (Ser9) GSK-3␤ were reduced in muscles from septic rats, consistent with activation of the kinase, and in the same study, treatment of septic muscles with GSK-3␤ inhibitors reduced protein breakdown.…”

Section: Calpain Activation Downregulates Akt Activity In Skeletal Musupporting

confidence: 77%

“…Thus, in a recent study (31) we found that muscle levels of phosphorylated (Ser9) GSK-3␤ were reduced in muscles from septic rats, consistent with activation of the kinase, and in the same study, treatment of septic muscles with GSK-3␤ inhibitors reduced protein breakdown. In another study (32), burn-induced muscle proteolysis was associated with activation of GSK-3␤ determined as reduced p(Ser9)-GSK-3␤ levels and increased GSK-3␤ kinase activity. Reduced phosphorylation and activity of mTOR, downstream of inhibited Akt activity, are important for the development of muscle wasting mainly by inhibition of protein synthesis (61).…”

Section: Calpain Activation Downregulates Akt Activity In Skeletal Mumentioning

confidence: 95%

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Calpain activity and muscle wasting in sepsis

Smith¹,

Lecker²,

Hasselgren³

2008

American Journal of Physiology-Endocrinology and Metabolism

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108

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Smith IJ, Lecker SH, Hasselgren PO. Calpain activity and muscle wasting in sepsis. Am J Physiol Endocrinol Metab 295: E762-E771, 2008. First published May 20, 2008 doi:10.1152/ajpendo.90226.2008.-Muscle wasting in sepsis reflects activation of multiple proteolytic mechanisms, including lyosomal and ubiquitin-proteasome-dependent protein breakdown. Recent studies suggest that activation of the calpain system also plays an important role in sepsis-induced muscle wasting. Perhaps the most important consequence of calpain activation in skeletal muscle during sepsis is disruption of the sarcomere, allowing for the release of myofilaments (including actin and myosin) that are subsequently ubiquitinated and degraded by the 26S proteasome. Other important consequences of calpain activation that may contribute to muscle wasting during sepsis include degradation of certain transcription factors and nuclear cofactors, activation of the 26S proteasome, and inhibition of Akt activity, allowing for downstream activation of Foxo transcription factors and GSK-3␤. The role of calpain activation in sepsis-induced muscle wasting suggests that the calpain system may be a therapeutic target in the prevention and treatment of muscle wasting during sepsis. Furthermore, because calpain activation may also be involved in muscle wasting caused by other conditions, including different muscular dystrophies and cancer, calpain inhibitors may be beneficial not only in the treatment of sepsis-induced muscle wasting but in other conditions causing muscle atrophy as well. muscle proteolysis; calcium; atrophy; calpastatin LOSS OF MUSCLE MASS IS COMMONLY seen in patients with sepsis (44, 55). Several other catabolic conditions, such as burn injury, cancer, uremia, and AIDS, are also associated with muscle wasting (20,27,29,79). Muscle wasting has several significant clinical consequences. For example, loss of muscle mass results in weakness and fatigue, in turn resulting in delayed ambulation and prolonged rehabilitation. When patients are bedridden for long periods of time, the risks for thromboembolic events as well as for pneumonia and other pulmonary complications increase. Prolonged bed rest in itself causes loss of muscle mass, thus creating a vicious cycle (35). Patients treated in the intensive care unit may need ventilatory support for extended periods of time when respiratory muscles are atrophying (82).Under normal conditions, muscle mass is maintained by a balance between protein synthesis and degradation, and muscle wasting can occur in any situation when this equilibrium is perturbed. There is evidence that loss of muscle mass during sepsis to a great extent reflects activated breakdown of muscle proteins, in particular the contractile proteins actin and myosin (48), but reduced protein synthesis may also contribute to sepsis-induced muscle wasting (62).Although increased expression and activity of the ubiquitinproteasome proteolytic pathway, including a dramatic upregulation of the muscle-specific ubiquitin ligases atrogin-1 and M...

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Section: Calpain Activation Downregulates Akt Activity In Skeletal Musupporting

confidence: 77%

Section: Calpain Activation Downregulates Akt Activity In Skeletal Mumentioning

confidence: 95%

Calpain activity and muscle wasting in sepsis

Smith¹,

Lecker²,

Hasselgren³

2008

American Journal of Physiology-Endocrinology and Metabolism

Self Cite

108

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show abstract

“…Studies in skeletal muscles have linked GSK-3b to muscle-wasting conditions. GSK-3b activity has been shown to increase in aged (Kinnard et al, 2005) and burn-injured skeletal muscles (Fang et al, 2007). Inhibition of GSK-3b is required for IGF-1-induced myogenic differentiation (Vyas et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Suppression of GSK-3β activation by M-cadherin protects myoblasts against mitochondria-associated apoptosis during myogenic differentiation

Wang

Hao

2011

Journal of Cell Science

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Apoptosis occurs concurrently with differentiation of muscle progenitor cells (MPCs) before they fuse to form myotubes. Dysregulated apoptosis in MPCs contributes to the low regeneration capability in aged muscle and decreases the survival rate of donor cells in stem cell-based therapies for muscular dystrophies. This study investigated the role of the M-cadherin/PI3K/Akt/GSK-3β signaling pathway in regulating apoptosis during differentiation of MPCs. Disruption of M-cadherin-dependent cell-cell adhesion by M-cadherin RNA interference in confluent C2C12 myoblasts sensitized the cells to mitochondria-associated intrinsic apoptosis induced by cell confluence or serum starvation. Further investigation of this pathway revealed that M-cadherin-mediated signaling suppressed GSK-3β activation by enhancing the PI3K/AKT-dependent inhibitory phosphorylation of Ser9 in GSK-3β. Overexpression of wild-type GSK-3β in confluent C2C12 myoblasts exacerbated the apoptosis, whereas chemical inhibition of GSK-3β using TDZD-8, or forced expression of constitutively active Akt (myrAkt), or a kinase-deficient GSK-3β mutant [GSK-3β(K85R)], attenuated apoptosis and rescued the impaired myogenic differentiation that is caused by M-cadherin RNA interference. These data suggest that M-cadherin-mediated signaling prevents acceleration of mitochondria-associated intrinsic apoptosis in MPCs by suppressing GSK-3β activation during myogenic differentiation.

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“…The activation of Akt signal has an antiapoptotic/ survival and cytoprotective functions in skeletal muscle cells (Conejo and Lorenzo 2001;Lawlor and Rotwein 2000). It has been also reported that the inhibition of GSK3 , which is induced by the phosphorylation, facilitates the diVerentiation of muscle cells (Fang et al 2005;Fang et al 2007;van der Velden et al 2006;van der Velden et al 2007;Vyas et al 2002). Recently, it was reported that the administration of G-CSF could reduce apoptosis in injured skeletal muscle (Stratos et al 2007).…”

Section: Discussionmentioning

confidence: 99%

Administration of granulocyte colony-stimulating factor facilitates the regenerative process of injured mice skeletal muscle via the activation of Akt/GSK3αβ signals

et al. 2008

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Effects of administration of granulocyte colony-stimulating factor (G-CSF) on the regeneration of injured mammalian skeletal muscles were studied in male C57BL/6J mice. Muscle injury was induced by injection of cardiotoxin (CTX) into tibialis anterior muscles bilaterally. G-CSF was administrated for 8 consecutive days from 3 days before and 5 days after the injection. Significant decreases of wet weight and protein content were noted in the necrotic muscle with CTX injection. A large number of the regenerating fibers having central nucleus were observed 7 days after the injection. The regeneration of injured muscle was further facilitated by the G-CSF treatment. Population of Pax7-positive nuclei was increased by the G-CSF treatment at day 7. Phospho-Akt and phospho-glycogen synthase kinase 3alphabeta (GSK3alphabeta) signals were also activated by G-CSF-administrated group during the regenerative process. It was suggested that G-CSF treatment may facilitate the regeneration of injured skeletal muscles via the activation of Akt/GSK3alphabeta signals.

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GSK-3β activity is increased in skeletal muscle after burn injury in rats

Cited by 24 publications

References 38 publications

Calpain activity and muscle wasting in sepsis

Calpain activity and muscle wasting in sepsis

Suppression of GSK-3β activation by M-cadherin protects myoblasts against mitochondria-associated apoptosis during myogenic differentiation

Administration of granulocyte colony-stimulating factor facilitates the regenerative process of injured mice skeletal muscle via the activation of Akt/GSK3αβ signals

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