Stress and Signaling Responses of Rat Skeletal Muscle to Brief Endurance Exercise During Hindlimb Unloading: a Catch-Up Process for Atrophied Muscle

Gwag, Taesik; Lee, Kisoo; Ju, Honglyoul; Shin, Haksup; Lee, Ju-Woon; Choi, Inho

doi:10.1159/000257510

Cited by 40 publications

(21 citation statements)

References 34 publications

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“…6B), indicating increased FoxO3a activity. This result is consistent with previous reports (25,65). On the other hand, no change in the expression of phosphorylated FoxO3a at Ser 253 was observed during unloading in the suppression of AMPK activity (Fig.…”

Section: Discussionsupporting

confidence: 94%

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: Discussionsupporting

confidence: 94%

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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“…For example, it has been shown that 14-day HS induces a significant reduction in phosphorylated AKT (Ser473) [19,20], p70s6k (Thr389) [19][20][21] and 4E-BP1 [19] in rat soleus muscle. At the same time, some authors did not find an increase in phosphorylated p70s6k (Thr389) in soleus after 10 days of mechanical unloading [22].…”

Section: Introductionmentioning

confidence: 99%

Key Markers of mTORC1-Dependent and mTORC1-Independent Signaling Pathways Regulating Protein Synthesis in Rat Soleus Muscle During Early Stages of Hindlimb Unloading

Mirzoev

Tyganov²,

Vilchinskaya³

et al. 2016

Cell Physiol Biochem

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Background/Aims: The purpose of the study was to assess the amount of rRNA and phosphorylation status of the key markers of mTORC1-dependent (70s6k, 4E-BP1) and mTORC1-independent (GSK-3β, AMPK) signaling pathways controlling protein synthesis in rat soleus during early stages of mechanical unloading (hindlimb suspension (HS) for 1-, 3- and 7 days). Methods: The content of the key signaling molecules of various anabolic signaling pathways was determined by Western-blotting. The amount of 28S rRNA was evaluated by RT-PCR. The rate of protein synthesis was assessed using in-vivo SUnSET technique. Results: HS for 3 and 7 days induced a significant (p<0.05) decrease in the rate of global protein synthesis in soleus muscle in comparison with control. HS within 24 hours resulted in a significant (p<0.05) decrease in p-4E-BP1 content, p-AMPK content and increase in p-p70s6k content in rat soleus muscle. Following three days of HS the content of p-AKT was decreased (p<0.05). After 7 days of HS the phosphorylation level of AKT and GSK-3beta was significantly reduced (p<0.05) compared to control. We also observed a significant decrease in the amount of 28S rRNA in rat soleus following 1, 3 and 7 days of HS. Conclusion: Taken together, the results of our study suggest that a decline in the global rate of protein synthesis in rat soleus during early stages of simulated microgravity is associated with impaired ribosome biogenesis as well as reduced activity of mTORC1-independent signaling pathways.

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“…1,2) Skeletal muscle cells are susceptible to oxidative stress induced through electron transport and oxygen flux during normal contraction, and this stress may increase with exercise intensity. [1][2][3][4][5][6] Muscle redox status, especially during atrophy, is more oxidative than the redox status in other organs. Augmentation of cellular antioxidant defense presents a basic strategy for controlling oxidative muscle injury and related disease conditions.…”

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confidence: 99%

Sauchinone Attenuates Oxidative Stress-Induced Skeletal Muscle Myoblast Damage through the Down-Regulation of Ceramide

Jung

Song

Bae

et al. 2011

Biological & Pharmaceutical Bulletin

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We investigated the effects of sauchinone, isolated from the root of Saururus chinensis, on muscle disorders and the underlying mechanism of oxidative stress-induced C 2 C 12 skeletal muscle myoblast damage. To assess the protective effects of sauchinone on oxidative stress-induced C 2 C 12 skeletal muscle myoblasts, we measured the viability of the cells, showing that sauchinone pre-treatment significantly reduced the decreased cell viability after H 2 O 2 treatment. We also investigated the mechanism of this protective effect of sauchinone. In Western blot analysis, the heat shock protein (HSP)-70 level increased significantly in the sauchinone-pretreated myoblasts. We used high performance liquid chromatography (HPLC) to examine the level of endogenous ceramide after pre-treatment with sauchinone followed by exposure to H 2 O 2 . While hydrogen peroxide increased the ceramide content to approximately 166.60؎ ؎38.93% of the control level, pre-treatment with sauchinone inhibited this increase, maintaining the ceramide content at the control level. We demonstrated that sauchinone regulates intracellular HSP70 expression as well as ceramide levels to protect against oxidative stress-induced C 2 C 12 muscle myoblast damage. We suggest the potential benefits of herbal medicines in the treatment of oxidative stressrelated muscle disorders.

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Stress and Signaling Responses of Rat Skeletal Muscle to Brief Endurance Exercise During Hindlimb Unloading: a Catch-Up Process for Atrophied Muscle

Cited by 40 publications

References 34 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

Key Markers of mTORC1-Dependent and mTORC1-Independent Signaling Pathways Regulating Protein Synthesis in Rat Soleus Muscle During Early Stages of Hindlimb Unloading

Sauchinone Attenuates Oxidative Stress-Induced Skeletal Muscle Myoblast Damage through the Down-Regulation of Ceramide

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