Tony kemp is correct about it not affecting the heart. It only affects the skeletal muscle and leaves cardiac and smooth alone.
Here is some info...I'll try to find the pics of the freaky mice also.
The myostatin propeptide and the follistatin-related gene are inhibitory binding proteins of myostatin in normal serum.
Hill JJ, Davies MV, Pearson AA, Wang JH, Hewick RM, Wolfman NM, Qiu Y.
Department of Protein Chemistry and Proteomics, Wyeth Research, 87 Cambridge Park Drive, Cambridge, MA 02140, USA.
[email protected]
Myostatin, also known as growth and differentiation factor 8, is a member of the transforming growth factor beta superfamily that negatively regulates skeletal muscle mass (1). Recent experiments have shown that myostatin activity is detected in serum by a reporter gene assay only after activation by acid, suggesting that native myostatin circulates as a latent complex (2). We have used a monoclonal myostatin antibody, JA16, to isolate the native myostatin complex from normal mouse and human serum. Analysis by mass spectrometry and Western blot shows that circulating myostatin is bound to at least two major proteins, the myostatin propeptide and the follistatin-related gene (FLRG). The myostatin propeptide is known to bind and inhibit myostatin in vitro (3). Here we show that this interaction is relevant in vivo, with a majority (>70%) of myostatin in serum bound to its propeptide. Studies with recombinant V5-His-tagged FLRG protein confirm a direct interaction between mature myostatin and FLRG. Functional studies show that FLRG inhibits myostatin activity in a reporter gene assay. These experiments suggest that the myostatin propeptide and FLRG are major negative regulators of myostatin in vivo.
PMID: 12194980 [PubMed - indexed for MEDLINE]
Deacetylase inhibitors increase muscle cell size by promoting myoblast recruitment and fusion through induction of follistatin.
Iezzi S, Di Padova M, Serra C, Caretti G, Simone C, Maklan E, Minetti G, Zhao P, Hoffman EP, Puri PL, Sartorelli V.
Muscle Gene Expression Group, Laboratory of Muscle Biology, NIAMS, National Institutes of Health, Bethesda, MD 20892, USA.
Fusion of undifferentiated myoblasts into multinucleated myotubes is a prerequisite for developmental myogenesis and postnatal muscle growth. We report that deacetylase inhibitors favor the recruitment and fusion of myoblasts into preformed myotubes. Muscle-restricted expression of follistatin is induced by deacetylase inhibitors and mediates myoblast recruitment and fusion into myotubes through a pathway distinct from those utilized by either IGF-1 or IL-4. Blockade of follistatin expression by RNAi-mediated knockdown, functional inactivation with either neutralizing antibodies or the antagonist protein myostatin, render myoblasts refractory to HDAC inhibitors. Muscles from animals treated with the HDAC inhibitor trichostatin A display increased production of follistatin and enhanced expression of markers of regeneration following muscle injury. These data identify follistatin as a central mediator of the fusigenic effects exerted by deacetylase inhibitors on skeletal muscles and establish a rationale for their use to manipulate skeletal myogenesis and promote muscle regeneration.
Effects of heavy resistance training on myostatin mRNA and protein expression.
Willoughby DS.
Exercise and Molecular Kinesiology Laboratory, Department of Kinesiology, Texas Christian University, Fort Worth, TX 76129, USA.
[email protected]
PURPOSE: Myostatin is a negative regulator of muscle mass and its effects seem to be exacerbated by glucocorticoids; however, its response to resistance training is not well known. This study examined 12 wk of resistance training on the mRNA and protein expression of myostatin, follistatin-like related gene (FLRG), activin IIb receptor, cortisol, glucocorticoid receptor, myofibrillar protein, as well as the effects on muscle strength and mass and body composition. METHODS: Twenty-two untrained males were randomly assigned to either a resistance-training [RTR (N = 12)] or control group [CON (N = 10)]. Muscle biopsies and blood samples were obtained before and after 6 and 12 wk of resistance training. RTR trained 3 x wk(-1) using three sets of six to eight repetitions at 85-90% 1-RM on lower-body exercises, whereas CON performed no resistance training. Data were analyzed with two- and three-way ANOVA. RESULTS: After 12 wk of training, RTR increased total body mass, fat-free mass, strength, and thigh volume and mass; however, they increased myostatin mRNA, myostatin, FLRG, cortisol, glucocorticoid receptor, and myofibrillar protein after 6 and 12 wk of training (P < 0.05). CONCLUSIONS: Resistance training and/or increased glucocorticoid receptor expression appears to up-regulate myostatin mRNA expression. Furthermore, it is possible that any plausible decreases in skeletal muscle function from the observed increase in serum myostatin were attenuated by increased serum FLRG levels and the concomitant down-regulation of the activin IIb receptor. It is therefore concluded that the increased myostatin in response to cortisol and/or resistance training appears to have no effects on training-induced increases in muscle strength and mass.
Follistatin complexes Myostatin and antagonises Myostatin-mediated inhibition of myogenesis.
Amthor H, Nicholas G, McKinnell I, Kemp CF, Sharma M, Kambadur R, Patel K.
Department of Veterinary Basic Sciences, Royal Veterinary College, London NW1 OTU, UK.
Follistatin is known to antagonise the function of several members of the TGF-beta family of secreted signalling factors, including Myostatin, the most powerful inhibitor of muscle growth characterised to date. In this study, we compare the expression of Myostatin and Follistatin during chick development and show that they are expressed in the vicinity or in overlapping domains to suggest possible interaction during muscle development. We performed yeast and mammalian two-hybrid studies and show that Myostatin and Follistatin interact directly. We further show that single modules of the Follistatin protein cannot associate with Myostatin suggesting that the entire protein is required for the interaction. We analysed the interaction kinetics of the two proteins and found that Follistatin binds Myostatin with a high affinity of 5.84 x 10(-10) M. We next tested whether Follistatin suppresses Myostatin activity during muscle development. We confirmed our previous observation that treatment of chick limb buds with Myostatin results in a severe decrease in the expression of two key myogenic regulatory genes Pax-3 and MyoD. However, in the presence of Follistatin, the Myostatin-mediated inhibition of Pax-3 and MyoD expression is blocked. We additionally show that Myostatin inhibits terminal differentiation of muscle cells in high-density cell cultures of limb mesenchyme (micromass) and that Follistatin rescues muscle differentiation in a concentration-dependent manner. In summary, our data suggest that Follistatin antagonises Myostatin by direct protein interaction, which prevents Myostatin from executing its inhibitory effect on muscle development.
Table 1: Antagonists of TGF-ß Ligands
Natural TGF-ß Antagonists Structural Features Contained in the Antagonist Polypeptide (M.W.) Known TGF-ß Binding Partners
Noggin Unique Noggin cysteine-knot domain (26 kDa) BMP-2,-4,-5,-6,-7, -13/GDF-6, -14/GDF-5
Chordin 4 CR/VWC (Chordin) domains, 3 SOG repeats (102 kDa) BMP-2,-4,-7
Chordin-like/neuralin/ventroptin 3 Chordin domains (51 kDa) BMP-4,-5,-6
Follistatin 3 Cysteine-rich Follistain (FS) and 3 kazal domains (38 kDa) Activin, BMP-2,-4,-6,-7, Myostatin/GDF-8, GDF-11, TGF-ß1
Follistatin-like related gene (FLRG) 2 FS and 2 kazal domains (28 kDa) Activin, Myostatin/GDF-8, GDF-11, TGF-ß1
GASP-1 1 Wap, 1 FS, 1 kazal, 1 IG-like, 2 kunitz, 1 netrin domains (63 kDa) Myostatin/GDF-8, GDF-11
Follistatin-related protein (FSRP) 1 FS, 1 CR/VWRC, 2 EF-hand domains (35 kDa) Activin, BMP-2,-6,-7
DAN Unique DAN cysteine-knot domain (19 kDa) BMP-2,-4,-7, -14/GDF-5
Cerberus DAN-like cysteine-knot domain (30 kDa) BMP-2,-4,-7, Activin, Nodal
Gremlin DAN-like cysteine-knot domain (21 kDa) BMP-2,-4,-7
Sclerostin /SOST Unique Sclerostin cysteine-knot domain (24 kDa) BMP-5,-6
Decorin Multiple leucine-rich repeats (40 kDa) TGF-ß1, -2
alpha-2 macroglobulin Multiple proteinase inhibitor domains (163 kDa) TGF-ß1, -2, Activin, Inhibin