Angiotensin II activates myostatin expression in cultured rat neonatal cardiomyocytes via p38 MAP kinase and myocyte enhance factor 2 pathway

Wang, Bao Wei; Chang, Hang; Kuan, Peiliang; Shyu, Kou‐Gi

doi:10.1677/joe-07-0596

Cited by 42 publications

(32 citation statements)

References 37 publications

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“…The initial activation of MSTN after myocardial ischemia that we report may be exerted in different manners. Myocyte stretch and angiotensin II can activate MSTN via IGF-1/p38 [10,25], and our data show that MSTN increase is accompanied by p38 activation. TNF-α, which is activated upon ischemia, can also be triggering MSTN activation.…”

Section: Discussionmentioning

confidence: 70%

Cardiac myostatin upregulation occurs immediately after myocardial ischemia and is involved in skeletal muscle activation of atrophy

Castillero

Akashi

Wang

et al. 2015

Biochemical and Biophysical Research Communications

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Myostatin (MSTN), a negative regulator of muscle growth and size, is increased after acute myocardial infarction (AMI) but timing of upregulation after injury is not known. In this study, we investigated the timing of the MSTN/AKT/p38 pathway activation in heart and skeletal muscle after AMI, as well as the potential effect of cardiac injury-related MSTN endocrine signaling on skeletal muscle and other circulating growth factors. Methods Coronary artery ligation was performed in C57BL/6 mice at age 8 weeks to induce AMI. Mice were sacrificed at different time points (10m, 1h, 2h, 6h, 12h, 24h, 1 week, 2 weeks, 1 months and 2 months) after surgery (n=3 per time point, n=18 total). Results Cardiac and circulating MSTN upregulation occurred as early as 10 minutes after AMI. Two months after AMI, increased cardiac MSTN/SMAD2,3 and p38 together with decreased IGF-1/AKT signaling suggest an anti-hypertrophic profile. In skeletal muscle, an absence of local MSTN increase was accompanied by increased MSTN-dependent SMAD2,3 signaling, suggestive of paracrine effects due to cardiac-derived MSTN. Protein degradation by the ubiquitin-proteasome system in the skeletal muscle was also evident. Serum from 24h post-MI mice effectively induced a MSTN-dependent increase in atrogin1 and MuRF1. Conclusion Our study shows that cardiac MTSN activation occurs rapidly after cardiac ischemia and may be involved in peripheral protein degradation in the skeletal muscle by activating atrogin1 and MuRF1.

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Section: Discussionmentioning

confidence: 70%

Cardiac myostatin upregulation occurs immediately after myocardial ischemia and is involved in skeletal muscle activation of atrophy

Castillero

Akashi

Wang

et al. 2015

Biochemical and Biophysical Research Communications

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“…MEF2 transcription factors are involved in the regulation of inducible gene expression during hypertrophy and MEF2 activity is increased during pressure or volume overload [43]. Activation of MEF2A and MEF2C is stimulated by p38; however, p38α may be more efficient than p38γ at activating MEF2 [44][45][46]. Expression of an active variant of p38γ attenuates, whereas active p38α induces, expression of AP-1-driven reporter genes [42].…”

Section: Discussionmentioning

confidence: 99%

Effect of pressure overload-induced hypertrophy on the expression and localization of p38 MAP kinase isoforms in the mouse heart

Dingar

Merlen

Grandy

et al. 2010

Cellular Signalling

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Abstractp38 mitogen-activated protein kinases (MAPKs) are serine/threonine specific protein kinases that respond to cellular stress and regulate a broad range of cellular activities. There are four major isoforms of p38MAPK:α, β, γ, and δ. To date, the prominent isoform in heart has been thought to be p38α. We examined the expression of each p38 isoform at both the mRNA and protein level in murine heart. mRNA for all four p38 isoforms was detected. p38γ and p38δ were expressed at protein levels comparable to p38α and 38β, respectively. In the early phase of pressure-overload hypertrophy (1-7 days after constriction of the transverse aorta), the abundance of p38β, p38γ and p38δ mRNA increased; however, no corresponding changes were detected at the protein level. Confocal immunofluorescence studies revealed p38α and p38γ in both the cytoplasm and nucleus. In the established phase of hypertrophy induced by chronic pressure overload (7-28 days after constriction of the transverse aorta), p38γ immunoreactivity accumulated in the nucleus whereas the distribution of p38α remained unaffected. Hence, both p38α and p38γ are prominent p38 isoforms in heart and p38γ may play a role in mediating the changes in gene expression associated with cardiac remodeling during pressure-overload hypertrophy.

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“…In vitro studies in isolated cardiomyocytes suggest that myostatin mRNA and protein can be directly induced in these cells by mechanical stretch or humoral stimulation with IGF-I, phenylephrine, or angiotensin II, involving intracellular activation of mitogen-activated protein kinases (p38 and/or ERK) and binding of the transcription factor MEF2 within the myostatin promoter region (15,74,87). One study failed to report an enhancement of cardiac myostatin mRNA during heart failure progression in dogs due to overpacing but instead detected elevated levels of the related activin-A in moderate and severe heart failure (2-to 3-fold increase) (47).…”

Section: Cardiac Myostatin In Health and Diseasementioning

confidence: 99%

Myostatin from the heart: local and systemic actions in cardiac failure and muscle wasting

Breitbart

Auger‐Messier

Molkentin

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

107

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A significant proportion of heart failure patients develop skeletal muscle wasting and cardiac cachexia, which is associated with a very poor prognosis. Recently, myostatin, a cytokine from the transforming growth factor-β (TGF-β) family and a known strong inhibitor of skeletal muscle growth, has been identified as a direct mediator of skeletal muscle atrophy in mice with heart failure. Myostatin is mainly expressed in skeletal muscle, although basal expression is also detectable in heart and adipose tissue. During pathological loading of the heart, the myocardium produces and secretes myostatin into the circulation where it inhibits skeletal muscle growth. Thus, genetic elimination of myostatin from the heart reduces skeletal muscle atrophy in mice with heart failure, whereas transgenic overexpression of myostatin in the heart is capable of inducing muscle wasting. In addition to its endocrine action on skeletal muscle, cardiac myostatin production also modestly inhibits cardiomyocyte growth under certain circumstances, as well as induces cardiac fibrosis and alterations in ventricular function. Interestingly, heart failure patients show elevated myostatin levels in their serum. To therapeutically influence skeletal muscle wasting, direct inhibition of myostatin was shown to positively impact skeletal muscle mass in heart failure, suggesting a promising strategy for the treatment of cardiac cachexia in the future.

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Angiotensin II activates myostatin expression in cultured rat neonatal cardiomyocytes via p38 MAP kinase and myocyte enhance factor 2 pathway

Cited by 42 publications

References 37 publications

Cardiac myostatin upregulation occurs immediately after myocardial ischemia and is involved in skeletal muscle activation of atrophy

Cardiac myostatin upregulation occurs immediately after myocardial ischemia and is involved in skeletal muscle activation of atrophy

Effect of pressure overload-induced hypertrophy on the expression and localization of p38 MAP kinase isoforms in the mouse heart

Myostatin from the heart: local and systemic actions in cardiac failure and muscle wasting

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