Disease relevance of Gdf8

• Concurrent treatment with RU-486 blocked dexamethasone-induced myostatin expression and significantly attenuated body loss and muscle atrophy [1].
• We found that the effect of dexamethasone on body weight and muscle loss and upregulation of intramuscular myostatin expression was time dependent [1].
• Rats that received dexamethasone showed significant body and muscle weight loss accompanied by an increase in intramuscular myostatin expression, compared with their saline-treated controls [2].
• These results are consistent with the hypothesis that the increased serum levels of active form of myostatin protein, induced yet unknown post-translational control mechanisms may be responsible, at least in part, for the muscle wasting associated with the adrenal insufficiency syndromes [3].
• Obtained results suggest that a high-protein diet leads to the high Mstn level to restrict muscle hypertrophy [4].
• To conclude, our study demonstrates that myostatin-induced muscle atrophy elicits the down-regulation of muscle-specific gene expression [5].

High impact information on Gdf8

• Our findings show that myostatin expression can be modulated in fully differentiated, nonpathological skeletal muscle in a manner that is inversely related to changes in muscle mass [6].
• Previous findings have provided strong evidence that myostatin functions as a negative regulator of muscle mass during development and growth [6].
• The stretch-induced myostatin is mediated by IGF-1 at least in part through a p38 MAP kinase and MEF2 pathway [7].
• Insulin-like growth factor-1 mediates stretch-induced upregulation of myostatin expression in neonatal rat cardiomyocytes [7].
• An in vivo model of aorta-caval shunt in adult rats also demonstrated the increased myostatin expression in the myocardium [7].

Chemical compound and disease context of Gdf8

• We hypothesized that glutamine effect on reversal of GC-induced muscle atrophy is mediated in part by suppression of myostatin [2].

Biological context of Gdf8

• Glucocorticoid-induced skeletal muscle atrophy is associated with upregulation of myostatin gene expression [1].
• Myostatin, activinR2b, and CDKI p21 were higher in the PCA animals (P < 0.05) [8].
• These data suggest that skeletal muscle atrophy seen in the portacaval shunted rats is a consequence of impaired satellite cell proliferation and differentiation mediated, in part, by higher myostatin and lower IGF1 expression [8].
• Quantitative reverse transcription/polymerase chain reaction demonstrated that myostatin gene expression was not altered by either cryolesion or CsA treatment combined with cryolesion [9].
• The increased cardiac growth in myostatin-null mice corresponded with increased p38 phosphorylation and Akt activation in vivo after phenylephrine treatment [10].

Anatomical context of Gdf8

• Skeletal muscle atrophy is associated with an increased expression of myostatin and impaired satellite cell function in the portacaval anastamosis rat [8].
• Both conditioned media from stretched myocytes and exogenous administration of IGF-1 recombinant protein to the non-stretched myocytes increased myostatin protein expression similar to that seen after cyclic stretch [7].
• Furthermore, crushed muscle extract prepared from regenerating skeletal muscle had induced myostatin mRNA expression in skeletal muscle-derived fibroblasts in a dose-dependent manner [11].
• In C2C12 myoblast cells, addition of glutamine to dexamethasone prevented the hyperexpression of myostatin induced by dexamethasone [2].
• RESULTS: No significant changes in IGF-I and GLUT4 mRNA levels were found in any of the muscles analysed. mRNA contents of myostatin were significantly reduced in gastrocnemius and vastus lateralis but not in soleus [12].

Associations of Gdf8 with chemical compounds

• The intramuscular myostatin concentration in rats treated with dexamethasone for 10 days returned to basal level [1].
• Treatment with carvedilol reversed both protein and mRNA of myocardial myostatin to the baseline values [13].
• Myostatin expression is not altered by insulin deficiency and replacement in streptozotocin-diabetic rat skeletal muscles [14].
• Treatment with N-acetylcysteine and doxazosin partially decreased myostatin mRNA and protein expression as compared with the shunt group [13].
• In situ hybridization analysis revealed that the cells positive for myostatin message were localized in the regenerating area of the bupivacaine-treated tissues, where a numerous number of mononucleated cells were present [11].

Other interactions of Gdf8

• We propose that dexamethasone-induced muscle loss is mediated, at least in part, by the upregulation of myostatin expression through a glucocorticoid receptor-mediated pathway [1].
• However, BC reversed the alcohol-induced increase in IGFBP-1 and muscle myostatin, known negative regulators of IGF-I action and muscle mass [15].
• Compared to control levels, myostatin transcripts were significantly elevated after only 0.5 h, myogenic regulatory factors significantly elevated after 3 h and desmin transcripts were significantly increased 12 h after EC [16].
• The myostatin-positive mononucleated cells contained both myogenic and nonmyogenic cells, as revealed by immunohistochemical staining for desmin and vimentin [11].
• MAIN OUTCOME MEASURES: The messenger ribonucleic acid (mRNA) levels of myoD, myostatin, and atrogin-1 were assessed by real-time polymerase chain reaction [17].

Analytical, diagnostic and therapeutic context of Gdf8

• However, the expression of myostatin in chronic heart failure resulting from volume-overload and after treatment with beta-blockers is little known [13].
• METHODS: We measured (Northern Blot) myostatin transcript levels in muscle groups with different fiber composition in streptozotocin-diabetic male rats receiving one of the following treatments for eight weeks: (1) control (C); (2) diabetes without treatment (DM); (3) diabetes with once-daily slow-acting insulin treatment (INS) [14].
• Myostatin expression was measured by Northern and Western blots, and was compared with glyceraldehyde-3-phosphate dehydrogenase [2].

References