Gravitational unloading inhibits the regenerative potential of atrophied soleus muscle in mice

Matsuba, Yusuke; Goto, Katsumasa; Morioka, Shigeta; Naito, Toshihito; Akema, Tatsuo; Hashimoto, Naohiro; Sugiura, T.; Ohira, Yoshinobu; Beppu, Masatoshi; Yoshioka, Toshitada

doi:10.1111/j.1748-1716.2008.01943.x

Cited by 48 publications

(62 citation statements)

References 38 publications

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“…The hindlimb suspension rodent model was developed to mimic spaceflight-associated skeletal muscle atrophy. Furthermore, antigravitational slow-twitch soleus muscle has been used the most frequently in the experiment of unloading (22,43,71,81) because it is comprised of more than 50% slow-twitch fiber (78), which is more affected by reduced weight-bearing. The molecular profiling of soleus muscle in response to hindlimb suspension has significance for understanding the underlying mechanism of unloading-and disuseassociated muscle atrophy.…”

Section: Discussionmentioning

confidence: 99%

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Involvement of AMPK in regulating slow-twitch muscle atrophy during hindlimb unloading in mice

Egawa

Goto

Ohno

et al. 2015

American Journal of Physiology-Endocrinology and Metabolism

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-AMPK is considered to have a role in regulating skeletal muscle mass. However, there are no studies investigating the function of AMPK in modulating skeletal muscle mass during atrophic conditions. In the present study, we investigated the difference in unloading-associated muscle atrophy and molecular functions in response to 2-wk hindlimb suspension between transgenic mice overexpressing the dominant-negative mutant of AMPK (AMPK-DN) and their wild-type (WT) littermates. Male WT (n ϭ 24) and AMPK-DN (n ϭ 24) mice were randomly divided into two groups: an untreated preexperimental control group (n ϭ 12 in each group) and an unloading (n ϭ 12 in each group) group. The relative soleus muscle weight and fiber cross-sectional area to body weight were decreased by ϳ30% in WT mice by hindlimb unloading and by ϳ20% in AMPK-DN mice. There were no changes in puromycin-labeled protein or Akt/70-kDa ribosomal S6 kinase signaling, the indicators of protein synthesis. The expressions of ubiquitinated proteins and muscle RING finger 1 mRNA and protein, markers of the ubiquitin-proteasome system, were increased by hindlimb unloading in WT mice but not in AMPK-DN mice. The expressions of molecules related to the protein degradation system, phosphorylated forkhead box class O3a, inhibitor of B␣, microRNA (miR)-1, and miR-23a, were decreased only in WT mice in response to hindlimb unloading, and 72-kDa heat shock protein expression was higher in AMPK-DN mice than in WT mice. These results imply that AMPK partially regulates unloading-induced atrophy of slow-twitch muscle possibly through modulation of the protein degradation system, especially the ubiquitin-proteasome system. AMP-activated protein kinase; protein degradation; autophagy; ubiquitin-proteasome; microRNA; heat shock protein SKELETAL MUSCLE IS THE LARGEST TISSUE IN THE BODY, accounting for ϳ40% of the total body mass, and has a crucial role in metabolism as well as locomotion. Skeletal muscle has a high ability to adapt to multiple stimuli. Increased loading, such as resistance training and mechanical stretching, leads to skeletal muscle hypertrophy (18,75). In contrast, aging, poor nutrition, several diseases such as diabetes, cancer, sepsis, and chronic renal failure, and decreased loading, such as inactivity, lead to skeletal muscle atrophy (23,34,39). Skeletal muscle atrophy occurs as a result of changes in protein turnover: decreased protein synthesis, increased protein degradation, or a combination of both (17). The coordination of protein turnover in the atrophic process is regulated by complicated molecular responses, and the molecular mechanism involved in this process in skeletal muscle is not yet completely understood and remains to be elucidated.5=-AMP-activated protein kinase (AMPK) is well established as a metabolic sensor that helps maintain cellular energy homeostasis by modulating glucose, lipid, and protein metabolism (16,26,28). AMPK is a heterotrimeric kinase comprising a catalytic ␣-subunit and two regulatory subunits, the ␤-and ␥-subunits. Two ...

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Section: Discussionmentioning

confidence: 99%

“…Mice in the unloading group were subjected to continuous hindlimb suspension for 2 wk. Hindlimb suspension was performed as described previously (43). Briefly, tails of the mice were cleaned and loosely surrounded by adhesive tapes cross-sectionally, fixing a string on the dorsal side of the tail, to keep the blood flow intact.…”

Section: Methodsmentioning

confidence: 99%

Involvement of AMPK in regulating slow-twitch muscle atrophy during hindlimb unloading in mice

Egawa

Goto

Ohno

et al. 2015

American Journal of Physiology-Endocrinology and Metabolism

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“…This idea originated from a number of studies that reported that the number of precursor cells decline in atrophied muscle [81–85]. More recent work supports this hypothesis by demonstrating that muscle atrophied by hindlimb suspension prior to cardiotoxin injury exhibited a block in regeneration that impairs any gain in muscle mass even six weeks following acute injury [86]. …”

Section: Introductionmentioning

confidence: 99%

Impaired regeneration: A role for the muscle microenvironment in cancer cachexia

Talbert

Guttridge

2016

Seminars in Cell & Developmental Biology

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While changes in muscle protein synthesis and degradation have long been known to contribute to muscle wasting, a body of literature has arisen which suggests that regulation of the satellite cell and its ensuing regenerative program are impaired in atrophied muscle. Lessons learned from cancer cachexia suggest that this regulation is simply not a consequence, but a contributing factor to the wasting process. In addition to satellite cells, evidence from mouse models of cancer cachexia also suggests that non-satellite progenitor cells from the muscle microenvironment are also involved. This chapter in the series reviews the evidence of dysfunctional muscle repair in multiple wasting conditions. Potential mechanisms for this dysfunctional regeneration are discussed, particularly in the context of cancer cachexia.

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“…A MENS-associated increase in Pax7-positive nuclei was also observed in the previous study 20) . The population of Pax7-positive nuclei increased in muscle following CTX-injectionassociated injury 31) . In the present study, a CTX injection-associated increase in the number of Pax7-positive nuclei was also observed.…”

Section: Effects Of Mensmentioning

confidence: 99%

“…The necrosis-regeneration cycle was induced by an intramuscular injection of CTX (100 µl, 10 µM in saline, Latoxan, France) into the proximal, middle, and distal regions of both the right and left tibialis anterior (TA) muscles except for C group, using a 27-gauge needle under anesthesia with the mice breathing isoflurane as described earlier [30][31][32] . The same volume of physiological saline was injected into both right and left TA muscles of mice in C group.…”

Section: Skeletal Muscle Injury Modelmentioning

confidence: 99%

Regeneration of Injured Tibialis Anterior Muscle in Mice in Response to Microcurrent Electrical Neuromuscular Stimulation with or without Icing

Yoshida

Fujiya

Goto

et al. 2015

J St. Marianna Univ

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Objective: Cold therapy, so-called icing, is often used immediately after muscle injuries as first aid for the suppression of inflammation and pain relief. Recent evidences show icing retards the regeneration of injured skeletal muscle. On the other hand, microcurrent electrical neuromuscular stimulation (MENS) promotes the regeneration of injured skeletal muscle. In this study, we investigated the effects of the MENS with or without icing on the regeneration of injured skeletal muscle. Methods: Eight-week-old male mice (C57BL/6J) were divided into 4 groups: control (C), cardiotoxin (CTX) injected (X), CTX injected with MENS (XM), and CTX injected with combined treatments with icing and MENS (XIM) groups. Necrosis-regeneration cycle was induced by an intramuscular injection of CTX into tibialis anterior (TA) muscles except for C group. After CTX-injection, the hindlimbs of the mice were soaked in ice-cold water (4ºC) for 20 minutes under anesthesia (XIM). After the treatments, both right and left hindlimbs of the mice in XIM and XM groups were treated with MENS (10 µA, 0.3 Hz, 250 msec) for 60 min a day and 3 days per week for 1 or 3 weeks. One and three weeks after CTX injection, TA muscles were dissected. Results: MENS with or without icing facilitated the recovery of muscle protein content and muscle fiber morphology including mean fiber cross-sectional areas of injured TA muscle, compared with non-treated condition. These facilitating effects of MENS with or without icing were accompanied with the increase in the relative number of Pax7-positive nuclei, namely satellite cells. Judging from fiber morphology, MENS with icing had enhanced stimulating effects on the regeneration of injured skeletal muscle, compared with MENS-treated condition. Conclusion: Evidence suggested that MENS with or without icing facilitated the regeneration of injured TA muscle. A combination treatment of MENS with icing might be a useful therapy for sports-related skeletal muscle injuries.

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Gravitational unloading inhibits the regenerative potential of atrophied soleus muscle in mice

Abstract: Results suggested that loading plays an important role in the activation of the regenerating potential of injured skeletal muscle.

Cited by 48 publications

References 38 publications

Involvement of AMPK in regulating slow-twitch muscle atrophy during hindlimb unloading in mice

Involvement of AMPK in regulating slow-twitch muscle atrophy during hindlimb unloading in mice

Impaired regeneration: A role for the muscle microenvironment in cancer cachexia

Regeneration of Injured Tibialis Anterior Muscle in Mice in Response to Microcurrent Electrical Neuromuscular Stimulation with or without Icing

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