Regulation of myosin heavy-chain gene expression during skeletal-muscle hypertrophy

Changes in the myosin phenotype of differentiated muscle are a prominent feature of the adaptation of the tissue to a variety of physiological stimuli. In the present study the molecular basis of changes in the proportion of myosin isoenzymes in rat skeletal muscle which occur during compensatory hypertrophy caused by the combined removal of synergist muscles and spontaneous running exercise was investigated. The relative amounts of sarcomeric myosin heavy (MHC)- and light (MLC)-chain mRNAs in the plantaris (fast) and soleus (slow) muscles from rats was assessed with cDNA probes specific for different MHC and MLC genes. Changes in the proportion of specific MHC mRNA levels were in the same direction as, and of similar magnitude to, changes in the proportion of myosin isoenzymes encoded for by the mRNAs. No significant changes in the proportion of MLC proteins or mRNA were detected. However, high levels of MLC3 mRNA were measured in both normal and hypertrophied soleus muscles which contained only trace amounts of MLC3 protein. Small amounts of embryonic and neonatal MHC mRNAs were induced in both muscles during hypertrophy. We conclude that the change in the pattern of myosin isoenzymes during skeletal-muscle adaptation to work overload is a consequence of changes in specific MHC mRNA levels.

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Hypertrophy of Rat Skeletal Muscle Is Associated with Increased SIRT1/Akt/mTOR/S6 and Suppressed Sestrin2/SIRT3/FOXO1 Levels

International Journal of Molecular Sciences ◽

10.3390/ijms22147588 ◽

2021 ◽

Vol 22 (14) ◽

pp. 7588

Author(s):

Zoltan Gombos ◽

Erika Koltai ◽

Ferenc Torma ◽

Peter Bakonyi ◽

Attila Kolonics ◽

...

Keyword(s):

Skeletal Muscle ◽

Muscle Hypertrophy ◽

Male Rats ◽

Cellular Interactions ◽

Molecular Signaling ◽

Protein Breakdown ◽

Rat Skeletal Muscle ◽

Plantaris Muscle ◽

Skeletal Muscle Hypertrophy ◽

Intensive Investigation

Despite the intensive investigation of the molecular mechanism of skeletal muscle hypertrophy, the underlying signaling processes are not completely understood. Therefore, we used an overload model, in which the main synergist muscles (gastrocnemius, soleus) of the plantaris muscle were surgically removed, to cause a significant overload in the remaining plantaris muscle of 8-month-old Wistar male rats. SIRT1-associated pro-anabolic, pro-catabolic molecular signaling pathways, NAD and H2S levels of this overload-induced hypertrophy were studied. Fourteen days of overload resulted in a significant 43% (p < 0.01) increase in the mass of plantaris muscle compared to sham operated animals. Cystathionine-β-synthase (CBS) activities and bioavailable H2S levels were not modified by overload. On the other hand, overload-induced hypertrophy of skeletal muscle was associated with increased SIRT1 (p < 0.01), Akt (p < 0.01), mTOR, S6 (p < 0.01) and suppressed sestrin 2 levels (p < 0.01), which are mostly responsible for anabolic signaling. Decreased FOXO1 and SIRT3 signaling (p < 0.01) suggest downregulation of protein breakdown and mitophagy. Decreased levels of NAD+, sestrin2, OGG1 (p < 0.01) indicate that the redox milieu of skeletal muscle after 14 days of overloading is reduced. The present investigation revealed novel cellular interactions that regulate anabolic and catabolic processes in the hypertrophy of skeletal muscle.

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Induction of Plasma Insulin by Dietary Sucrose Promotes Rat Skeletal Muscle Hypertrophy Under High-Protein Diets

Medicine & Science in Sports & Exercise ◽

10.1097/00005768-200405001-01549 ◽

2004 ◽

Vol 36 (Supplement) ◽

pp. S323

Author(s):

Hongsun Song ◽

Koichi Nakazato ◽

Hiroyuki Nakajima

Keyword(s):

Skeletal Muscle ◽

Plasma Insulin ◽

Muscle Hypertrophy ◽

High Protein ◽

Rat Skeletal Muscle ◽

Skeletal Muscle Hypertrophy ◽

High Protein Diets ◽

Protein Diets

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Ketogenic Diet and Skeletal Muscle Hypertrophy: a Frenemy Relationship?

Journal of Human Kinetics ◽

10.2478/hukin-2019-0071 ◽

2019 ◽

Vol 68 (1) ◽

pp. 233-247 ◽

Cited By ~ 1

Author(s):

Antonio Paoli ◽

Pasqualina Cancellara ◽

Pierluigi Pompei ◽

Tatiana Moro

Keyword(s):

Skeletal Muscle ◽

Ketogenic Diet ◽

Muscle Hypertrophy ◽

Scientific Evidence ◽

The Body ◽

Glucose Disposal ◽

Muscle Adaptation ◽

Total Body Mass ◽

Skeletal Muscle Hypertrophy ◽

Induce Weight Loss

AbstractKetogenic diet (KD) is a nutritional regimen characterized by a high-fat and an adequate protein content and a very low carbohydrate level (less than 20 g per day or 5% of total daily energy intake). The insufficient level of carbohydrates forces the body to primarily use fat instead of sugar as a fuel source. Due to its characteristic, KD has often been used to treat metabolic disorders, obesity, cardiovascular disease, and type 2 diabetes. Skeletal muscle constitutes 40% of total body mass and is one of the major sites of glucose disposal. KD is a well-defined approach to induce weight loss, with its role in muscle adaptation and muscle hypertrophy less understood. Considering this lack of knowledge, the aim of this review was to examine the scientific evidence about the effects of KD on muscle hypertrophy. We first described the mechanisms of muscle hypertrophy per se, and secondly, we discussed the characteristics and the metabolic function of KD. Ultimately, we provided the potential mechanism that could explain the influence of KD on skeletal muscle hypertrophy.

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COX-2 inhibitor reduces skeletal muscle hypertrophy in mice

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.90874.2008 ◽

2009 ◽

Vol 296 (4) ◽

pp. R1132-R1139 ◽

Cited By ~ 53

Author(s):

Margaret L Novak ◽

William Billich ◽

Sierra M. Smith ◽

Kunal B. Sukhija ◽

Thomas J. McLoughlin ◽

...

Keyword(s):

Skeletal Muscle ◽

Cell Proliferation ◽

Muscle Hypertrophy ◽

Muscle Growth ◽

Muscular Activity ◽

Compensatory Hypertrophy ◽

Cell Nuclei ◽

Skeletal Muscle Hypertrophy ◽

Cox 2 ◽

Macrophage Accumulation

Anti-inflammatory strategies are often used to reduce muscle pain and soreness that can result from high-intensity muscular activity. However, studies indicate that components of the acute inflammatory response may be required for muscle repair and growth. The hypothesis of this study was that cyclooxygenase (COX)-2 activity is required for compensatory hypertrophy of skeletal muscle. We used the synergist ablation model of skeletal muscle hypertrophy, along with the specific COX-2 inhibitor NS-398, to investigate the role of COX-2 in overload-induced muscle growth in mice. COX-2 was expressed in plantaris muscles during compensatory hypertrophy and was localized mainly in or near muscle cell nuclei. Treatment with NS-398 blunted the increases in mass and protein content in overloaded muscles compared with vehicle-treated controls. Additionally, the COX-2 inhibitor decreased activity of the urokinase type plasminogen activator, macrophage accumulation, and cell proliferation, all of which are required for hypertrophy after synergist ablation. Expression of insulin-like growth factor-1 and phosphorylation of Akt, mammalian target of rapamycin, and p70S6K were increased following synergist ablation, but were not affected by NS-398. Additionally, expression of atrogin-1 was reduced during hypertrophy, but was also not affected by NS-398. These results demonstrate that COX-2 activity is required for skeletal muscle hypertrophy, possibly through facilitation of extracellular protease activity, macrophage accumulation, and cell proliferation.

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Induction of Plasma Insulin by Dietary Sucrose Promotes Rat Skeletal Muscle Hypertrophy Under High-Protein Diets

Medicine & Science in Sports & Exercise ◽

10.1249/00005768-200405001-01549 ◽

2004 ◽

Vol 36 (Supplement) ◽

pp. S323

Author(s):

Hongsun Song ◽

Koichi Nakazato ◽

Hiroyuki Nakajima

Keyword(s):

Skeletal Muscle ◽

Plasma Insulin ◽

Muscle Hypertrophy ◽

High Protein ◽

Rat Skeletal Muscle ◽

Skeletal Muscle Hypertrophy ◽

High Protein Diets ◽

Protein Diets

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Hypoxia transiently affects skeletal muscle hypertrophy in a functional overload model

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00262.2011 ◽

2012 ◽

Vol 302 (5) ◽

pp. R643-R654 ◽

Cited By ~ 25

Author(s):

Thomas Chaillou ◽

Nathalie Koulmann ◽

Nadine Simler ◽

Adélie Meunier ◽

Bernard Serrurier ◽

...

Keyword(s):

Skeletal Muscle ◽

Signaling Pathways ◽

Muscle Hypertrophy ◽

Molecular Mechanisms ◽

Muscle Growth ◽

Female Rats ◽

Mrna Levels ◽

Hypertrophic Response ◽

Protein Levels ◽

Skeletal Muscle Hypertrophy

Hypoxia induces a loss of skeletal muscle mass, but the signaling pathways and molecular mechanisms involved remain poorly understood. We hypothesized that hypoxia could impair skeletal muscle hypertrophy induced by functional overload (Ov). To test this hypothesis, plantaris muscles were overloaded during 5, 12, and 56 days in female rats exposed to hypobaric hypoxia (5,500 m), and then, we examined the responses of specific signaling pathways involved in protein synthesis (Akt/mTOR) and breakdown (atrogenes). Hypoxia minimized the Ov-induced hypertrophy at days 5 and 12 but did not affect the hypertrophic response measured at day 56. Hypoxia early reduced the phosphorylation levels of mTOR and its downstream targets P70S6K and rpS6, but it did not affect the phosphorylation levels of Akt and 4E-BP1, in Ov muscles. The role played by specific inhibitors of mTOR, such as AMPK and hypoxia-induced factors (i.e., REDD1 and BNIP-3) was studied. REDD1 protein levels were reduced by overload and were not affected by hypoxia in Ov muscles, whereas AMPK was not activated by hypoxia. Although hypoxia significantly increased BNIP-3 mRNA levels at day 5, protein levels remained unaffected. The mRNA levels of the two atrogenes MURF1 and MAFbx were early increased by hypoxia in Ov muscles. In conclusion, hypoxia induced a transient alteration of muscle growth in this hypertrophic model, at least partly due to a specific impairment of the mTOR/P70S6K pathway, independently of Akt, by an undefined mechanism, and increased transcript levels for MURF1 and MAFbx that could contribute to stimulate the proteasomal proteolysis.

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