Myostatin up-regulation is associated with the skeletal muscle response to hypoxic stimuli

Hayot, Maurice; Rodriguez, Julie; Vernus, Barbara; Carnac, Gilles; Jean, E.; Allen, David L.; Goret, Lucie; Obert, Philippe; Candau, Robin; Bonnieu, Anne

doi:10.1016/j.mce.2010.09.008

Cited by 78 publications

(65 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Such results could have medical relevance for patients suffering from chronic obstructive pulmonary diseases (COPD). Skeletal muscle atrophy and weakness in these patients are partly attributed to hypoxia (52) and are associated with an activation of REDD1 (16) and myostatin (20). Our preliminary data support the notion that anabolic signals related to functional load are able to counteract the increased expression of these two repressors of muscle mass during hypoxia exposure.…”

Section: Perspectives and Significancesupporting

confidence: 78%

“…Here, we showed that myostatin, another negative regulator of muscle growth (3), was early activated by hypoxia in Ct muscles, but this upregulation was minimized by functional overload. This finding confirms the role played by hypoxia on myostatin expression (20), but it rejects its involvement in explaining the inhibitory effect of hypoxia on muscle hypertrophy.…”

Section: R651supporting

confidence: 67%

“…In vitro studies showed that the Akt/mTOR pathway could be inhibited by hypoxia exposure (12,27,31), but to our knowledge, only few in vivo studies reported that prolonged hypoxia exposure altered this signaling pathway in skeletal muscles (16). Myostatin, a mediator of muscle atrophy, has been shown to partly account for the hypoxia-induced effects on muscle mass (20). Moreover, although the UPS was stimulated in hypoxemic heart (43), it remained unaffected by hypoxia in skeletal muscle, at least after chronic exposure (16).…”

mentioning

confidence: 96%

See 2 more Smart Citations

Hypoxia transiently affects skeletal muscle hypertrophy in a functional overload model

Chaillou¹,

Koulmann²,

Simler³

et al. 2012

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

-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 P70 S6K 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/P70 S6K pathway, independently of Akt, by an undefined mechanism, and increased transcript levels for MURF1 and MAFbx that could contribute to stimulate the proteasomal proteolysis.

show abstract

Section: Perspectives and Significancesupporting

confidence: 78%

Section: R651supporting

confidence: 67%

mentioning

confidence: 96%

See 1 more Smart Citation

Hypoxia transiently affects skeletal muscle hypertrophy in a functional overload model

Chaillou¹,

Koulmann²,

Simler³

et al. 2012

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

show abstract

“…Indeed, chronic restriction of blood flow resulted in a drop in the myostatin content in rats (49). However, myostatin upregulation was associated with the skeletal muscle response to hypoxia-mimicking agents in vitro (50).…”

Section: Discussionmentioning

confidence: 99%

Serum myostatin levels are negatively associated with abdominal aortic calcification in older men: the STRAMBO study

Szulc¹,

Hofbauer²,

Rauner³

et al. 2012

European Journal of Endocrinology

View full text Add to dashboard Cite

Objective: To assess the association between abdominal aortic calcification (AAC) and serum levels of myostatin, a negative regulator of skeletal muscle mass, which has been implicated in the development of atherosclerotic lesions in mice. Design and patients: We assessed AAC semiquantitatively from the lateral spine scans obtained using dual energy X-ray absorptiometry in 1071 men aged 20-87 years. Serum myostatin levels were measured by an immunoassay that detects all myostatin forms. Results: Total myostatin serum levels did not differ between men with or without self-reported ischemic heart disease, hypertension, or diabetes mellitus. Total serum myostatin levels were higher in men with higher serum calcium levels and lower in men with higher serum concentrations of highly sensitive C-reactive protein. Men with AAC had lower myostatin levels compared with men without AAC. Prevalence of AAC (AAC score O0) was lower in the highest myostatin quartile compared with the three lower quartiles (P!0.05). After adjustment for confounders, odds of AAC (AAC score O0) were lower (ORZ0.62; 95% confidence interval (95% CI), 0.45-0.85; P!0.005) for the fourth myostatin quartile vs the three lower quartiles combined. In the sub-analysis of 745 men aged R60 years, the results were similar: AAC prevalence was lower in the highest myostatin quartile compared with the three lower quartiles combined (ORZ0.54; 95% CI, 0.38-0.78; P!0.001). Conclusions: In older men, total myostatin serum levels are inversely correlated with AAC. Further studies are needed to investigate mechanisms underlying this association and to assess utility of myostatin as a cardiovascular marker.

show abstract

“…Previous research has demonstrated that chronic exposure to hypoxia adversely affects protein kinase B/mTOR signalling [123], up-regulates myostatin expression [124], and subsequently leads to atrophy in skeletal muscle [125].…”

Section: Intramuscular Signalling Pathwaysmentioning

confidence: 99%

Hypoxia and Resistance Exercise: A Comparison of Localized and Systemic Methods

et al. 2014

View full text Add to dashboard Cite

It is generally believed that optimal hypertrophic and strength gains are induced through moderate-or high-intensity resistance training, equivalent at least 60% of an individual's 1-repetition maximum (1RM). However, recent evidence suggests that similar adaptations are facilitated when low-intensity resistance exercise (~20-50% 1RM) is combined with blood flow restriction (BFR) to the working muscles. Although the mechanisms underpinning these responses are not yet firmly established, it appears that localized hypoxia created by BFR may provide an anabolic stimulus by enhancing the metabolic and endocrine response, and increase cellular swelling and signalling function following resistance exercise. Moreover, BFR has also been demonstrated to increase type II muscle fibre recruitment during exercise.However, inappropriate implementation of BFR can result in detrimental effects, including petechial haemorrhage and dizziness. Further, as BFR is limited to the limbs, the muscles of the trunk are unable to be trained under localized hypoxia. More recently, the use of systemic hypoxia via hypoxic chambers and devices has been investigated as a novel way to stimulate similar physiological responses to resistance training as BFR techniques. While little evidence is available, reports indicate that beneficial adaptations, similar to those induced by BFR, are possible using these methods. The use of systemic hypoxia allows large groups to train concurrently within a hypoxic chamber using multi-joint exercises. However, further scientific research is required to fully understand the mechanisms that cause augmented muscular changes during resistance exercise with a localized or systemic hypoxic stimulus.3

show abstract

Myostatin up-regulation is associated with the skeletal muscle response to hypoxic stimuli

Cited by 78 publications

References 66 publications

Hypoxia transiently affects skeletal muscle hypertrophy in a functional overload model

Hypoxia transiently affects skeletal muscle hypertrophy in a functional overload model

Serum myostatin levels are negatively associated with abdominal aortic calcification in older men: the STRAMBO study

Hypoxia and Resistance Exercise: A Comparison of Localized and Systemic Methods

Contact Info

Product

Resources

About