Akt/protein kinase B in skeletal muscle physiology and pathology

Wu, Mingquan; Falasca, Marco; Blough, Eric R.

doi:10.1002/jcp.22353

Cited by 48 publications

(44 citation statements)

References 99 publications

(208 reference statements)

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“…Regulation of musclin transcription has been linked to Akt activation (4,6,15,16). Akt is a serine/threonine kinase that has emerged as a critical signaling component for the regulation of cellular metabolism, growth, and survival in multiple systems (17). Akt activity is increased in response to numerous stimuli, including a wide variety of growth factors and hormones activating phosphatidylinositol 3-kinase (PI3-kinase) (18)(19)(20).…”

Section: Resultsmentioning

confidence: 99%

Musclin is an activity-stimulated myokine that enhances physical endurance

Subbotina

Sierra

Zhu

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

146

154

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Exercise remains the most effective way to promote physical and metabolic wellbeing, but molecular mechanisms underlying exercise tolerance and its plasticity are only partially understood. In this study we identify musclin-a peptide with high homology to natriuretic peptides (NP)-as an exercise-responsive myokine that acts to enhance exercise capacity in mice. We use human primary myoblast culture and in vivo murine models to establish that the activity-related production of musclin is driven by Ca 2+ -dependent activation of Akt1 and the release of musclin-encoding gene (Ostn) transcription from forkhead box O1 transcription factor inhibition. Disruption of Ostn and elimination of musclin secretion in mice results in reduced exercise tolerance that can be rescued by treatment with recombinant musclin. Reduced exercise capacity in mice with disrupted musclin signaling is associated with a trend toward lower levels of plasma atrial NP (ANP) and significantly smaller levels of cyclic guanosine monophosphate (cGMP) and peroxisome proliferator-activated receptor gamma coactivator 1-α in skeletal muscles after exposure to exercise. Furthermore, in agreement with the established musclin ability to interact with NP clearance receptors, but not with NP guanyl cyclase-coupled signaling receptors, we demonstrate that musclin enhances cGMP production in cultured myoblasts only when applied together with ANP. Elimination of the activity-related musclin-dependent boost of ANP/ cGMP signaling results in significantly lower maximum aerobic capacity, mitochondrial protein content, respiratory complex protein expression, and succinate dehydrogenase activity in skeletal muscles. Together, these data indicate that musclin enhances physical endurance by promoting mitochondrial biogenesis.osteocrin | mitochondria | skeletal muscle | exercise | natriuretic peptide

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Section: Resultsmentioning

confidence: 99%

Musclin is an activity-stimulated myokine that enhances physical endurance

Subbotina

Sierra

Zhu

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

146

154

View full text Add to dashboard Cite

show abstract

“…As a statistical significance, results of one-factor ANOVA were used: # p<0.05, ### p<0.001 vs. young rats; *p<0.05, **p<0.01, ***p<0.001 vs. old non-ferulate-fed rats, respectively levels in different aged tissues. For example, both Akt protein levels and activity are generally reduced in insulin-resistant or aged muscle (Wu et al 2011). Another reported that phosphorylation of Akt at Ser 473 and Thr 308 was higher in the soleus muscles of very old rats (33 months) compared with 6-and 27-month-old rats (Wu et al 2009).…”

Section: Discussionmentioning

confidence: 99%

Attenuation of age-related changes in FOXO3a activity and the PI3K/Akt pathway by short-term feeding of ferulate

Choi

Kim

Lee

et al. 2011

AGE

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Ferulate (4-hydroxy-3-methoxycinnamic acid) is a well-known phenolic compound that scavenges free radicals and exerts anti-inflammatory effects. Forkhead box O3a (FOXO3a), a transcription factor that plays important roles in aging processes, decreases with age and is negatively regulated through phosphorylation by phosphatidylinositol 3-kinase (PI3K)/Akt signaling. The present study investigated the efficacy of short-term ferulate feeding on age-related changes in PI3K/Akt/FOXO3a and upstream insulin signaling pathways in aged rats. In addition, changes in manganese superoxide dismutase (MnSOD) and catalase expression were examined because of their dependence on PI3K/Akt/FOXO3a activity. Short-term feeding experiments were done with a diet containing ferulate that was given to aged rats at doses of 3 or 6 mg kg −1 day −1 for 10 days.Results showed that FOXO3a activity was increased in the ferulate-fed old group compared with the control old group. Also, ferulate suppressed the PI3K/Akt signaling pathway that is responsible for FOXO3a inhibition in aged rats. Plasma insulin levels and the upstream insulin signaling pathway were also modulated by ferulate correspondingly with PI3K/ Akt/FOXO3a activity. The age-related decrease in two major antioxidant enzymes, MnSOD and catalase, was blunted by ferulate, which was accompanied by FOXO3a transcriptional activity. The significance of the present study is the finding that short-term feeding of ferulate effectively modulates age-related renal FOXO3a, PI3K/Akt and insulin signaling pathways, and MnSOD and catalase expression, all of which may be beneficial for attenuating the aging process.

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“…Although the three isoforms are expressed ubiquitously in mammals, their expression level varies depending on the cell type. Akt1 is expressed in all tissues, whereas Akt2 is enriched in insulin-sensitive tissues, such as muscle, adipose tissue and liver (Wu et al, 2011). Akt3 is preferentially expressed in brain, pancreas, lung and kidney.…”

Section: The Complex Relationship Between Notch Wnt and Hypoxiamentioning

confidence: 99%

Regulation of myogenesis by environmental hypoxia

Beaudry

Hidalgo

Launay

et al. 2016

Journal of Cell Science

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In aerobic organisms, oxygen is a critical factor for tissue and organ morphogenesis from embryonic development throughout the adult life. It regulates various intracellular pathways involved in cellular metabolism, proliferation, cell survival and fate. Organisms or tissues rapidly respond to changes in oxygen availability by activating complex signalling networks, which culminate in the control of mRNA translation and/or gene expression. This Commentary presents the effects of hypoxia during embryonic development, myoblasts and satellite cell proliferation and differentiation in vertebrates. We also outline the relationship between Notch, Wnt and growth factor signalling pathways, as well as the posttranscriptional regulation of myogenesis under conditions of hypoxia.

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Akt/protein kinase B in skeletal muscle physiology and pathology

Cited by 48 publications

References 99 publications

Musclin is an activity-stimulated myokine that enhances physical endurance

Musclin is an activity-stimulated myokine that enhances physical endurance

Attenuation of age-related changes in FOXO3a activity and the PI3K/Akt pathway by short-term feeding of ferulate

Regulation of myogenesis by environmental hypoxia

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