Longitudinal characterization of functional, morphologic, and biochemical adaptations in mouse skeletal muscle with hindlimb suspension

Hanson, Andrea; Harrison, Brooke C.; Young, Mary; Stodieck, Louis S.; Ferguson, Virginia L.

doi:10.1002/mus.23753

Cited by 46 publications

(71 citation statements)

References 35 publications

(91 reference statements)

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“…An additional aim of this study was to investigate the effects of testosterone on the gene and protein expression levels of some muscle hypertrophy and atrophy molecular targets after TS. TS resulted in downregulation of Igf1 mRNA in the SOL and EDL, an effect reported previously . We also showed that this effect was induced more rapidly in EDL muscle than in SOL muscle, suggesting that IGF‐1 may contribute more to initiation of the muscle loss in fast‐twitch than in slow‐twitch muscles during TS.…”

Section: Discussionsupporting

confidence: 82%

Effects of tail suspension on serum testosterone and molecular targets regulating muscle mass

et al. 2015

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TS produced an increase followed by a transient drop in testosterone levels. Muscle atrophy was associated with downregulation of Igf1 and upregulation of Mstn, Redd1, Atrogin-1, and MuRF1 mRNA with clear differences in Igf1, Mstn, and MAFbx/Atrogin-1 gene expression between SOL and EDL. Testosterone supplementation did not affect muscle mass or protein expression levels during TS. Conclusions The known anabolic effects of testosterone are not sufficient to ameliorate loss of muscle mass during TS.

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Section: Discussionsupporting

confidence: 82%

Effects of tail suspension on serum testosterone and molecular targets regulating muscle mass

et al. 2015

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“…In our experiments, VX-745 treatment prevented increase of the ubiquitin expression during unloading. Expression of muscle-specific E3 ubiquitin ligases MAFbx and MuRF1 is activated shortly after unloading and peaks at the third day [16,26]. VX-745 treatment prevented unloading-induced increase in MuRF-1, whereas MAFbx expression was not affected.…”

Section: Discussionmentioning

confidence: 96%

P38α-MAPK Signaling Inhibition Attenuates Soleus Atrophy during Early Stages of Muscle Unloading

Belova

Mochalova

Kostrominova

et al. 2020

IJMS

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To test the hypothesis that p38α-MAPK plays a critical role in the regulation of E3 ligase expression and skeletal muscle atrophy during unloading, we used VX-745, a selective p38α inhibitor. Three groups of rats were used: non-treated control (C), 3 days of unloading/hindlimb suspension (HS), and 3 days HS with VX-745 inhibitor (HSVX; 10 mg/kg/day). Total weight of soleus muscle in HS group was reduced compared to C (72.3 ± 2.5 vs 83.0 ± 3 mg, respectively), whereas muscle weight in the HSVX group was maintained (84.2 ± 5 mg). The expression of muscle RING-finger protein-1 (MuRF1) mRNA was significantly increased in the HS group (165%), but not in the HSVX group (127%), when compared with the C group. The expression of muscle-specific E3 ubiquitin ligases muscle atrophy F-box (MAFbx) mRNA was increased in both HS and HSVX groups (294% and 271%, respectively) when compared with C group. The expression of ubiquitin mRNA was significantly higher in the HS (423%) than in the C and HSVX (200%) groups. VX-745 treatment blocked unloading-induced upregulation of calpain-1 mRNA expression (HS: 120%; HSVX: 107%). These results indicate that p38α-MAPK signaling regulates MuRF1 but not MAFbx E3 ligase expression and inhibits skeletal muscle atrophy during early stages of unloading.

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“…Briefly, skeletal muscle from forelimbs and hind limbs of 2-to 3-weekold IR fl/fl Igf1r fl/fl mice was minced and digested in 2.5 mM CaCl 2 with 2.4 U/ml dispase (Grade II; Roche) and 1% collagenase B (Roche) for 20 minutes, with gentle pipetting twice. Homogenates were centrimRNA levels in fed MIGIRKOs and even observe a decrease in E3-ligase mRNA levels in muscle from fasted MIGIRKOs relative to controls, this is not unexpected, since models of chronic muscle atrophy (>21 days denervation, immobilization, or long-term spinal cord injury) in both humans and mice display no change or even a decrease in the key atrophy markers atrogin-1 and MuRF-1 (33)(34)(35)(36). However, FoxOs are the critical targets of IR/IGF1R, as deletion of these proteins rescued muscle atrophy and decreased E3-ligase expression.…”

Section: Primary Mouse Myoblast Isolationmentioning

confidence: 94%

Insulin and IGF-1 receptors regulate FoxO-mediated signaling in muscle proteostasis

O’Neill

Lee

Klaus

et al. 2016

Journal of Clinical Investigation

142

154

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Longitudinal characterization of functional, morphologic, and biochemical adaptations in mouse skeletal muscle with hindlimb suspension

Abstract: Insight into these early changes in response to HS improves understanding of the molecular and functional changes that lead to muscle atrophy.

Cited by 46 publications

References 35 publications

Effects of tail suspension on serum testosterone and molecular targets regulating muscle mass

Effects of tail suspension on serum testosterone and molecular targets regulating muscle mass

P38α-MAPK Signaling Inhibition Attenuates Soleus Atrophy during Early Stages of Muscle Unloading

Insulin and IGF-1 receptors regulate FoxO-mediated signaling in muscle proteostasis

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