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Follistatin - Myostatin (GDF-8) binder

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  • Follistatin - Myostatin (GDF-8) binder

    I originally made a post about myostatin binders at: http://forums.steroid.com/showthread...46#post1104246

    Has anyone heard about follistatin being used in bb, and if so any results???

    HUMAN Cytokine/Growth Factor/Chemokines Sample Spec sheets (subject to change without notice):


    --------------------------------------------------------------------------------
    DATA SHEET:Human Follistatin
    Follistatin belongs to a group of structurally-diverse diffusible proteins that binds to TGF-beta ligands and inhibit their activity by hindering access to signaling receptors. This naturally occurring antagonist binds to Activin, BMP-2,-4,-6,-7, Myostatin, GDF-11, and TGF-beta1. Follistatin is expressed in the pituitary, ovaries, decidual cells of the endometrium, and in some other tissues. This recombinant human Follistatin is a 31.5 kDa protein containing 288 amino acids including 36 cysteine residues.

    Package Size: 20 micrograms $xxx

    1 X 500ug=$x,xxx

    1mg=$x,xxx

    Mini-Pack:$xx/5ug

    -inquire for custom sizes/bulk packaging

    Supplied: The sterile filtered solution was lyophilized from 10mM sodium Phosphate pH7.5 + 75mM NaCl with no additives

    Source: E. coli

    Purity: >95% by SDS-Page and HPLC analysis Endotoxin <1EU/ug

    Reconstitution: The lyophilized human Follistatin should be reconstituted in sterile DI water to a concentration of 0.1-1mg/ml. Allow to set at least 30 minutes at 4-8 DEG C, Mix well. If desired, centrifuge for 1-2 minutes at 1000 rpm to concentrate material in vial. . This solution can be diluted into other buffered solutions and stored at 4 DEG C for up to 1 week or stored at -20 DEG C for future use.

    Note: If this material is not to be used for coating or labeling (or other applications requiring carrier free material), the addition of 0.1% BSA to further dilution buffers or dilution in sterile culture media is recommended to enhance stability and minimize absorption to vial. Ideally, maintain stock >10ug/ml.

    Storage: The lyophilized powder is stable at room temperature for a few weeks but it is best stored desiccated at -20 Deg C. Reconstituted material should be stored in working aliquots at -20DEG C. AVOID FREQUENT FREEZE THAW CYCLES.

    AA Sequence:

    GNCWLRQAKN GRCQVLYKTE LSKEECCSTG RLSTSWTEED VNDNTLFKWM

    IFNGGAPNCI PCKETCENVD CGPGKKCRMN KKNKPRCVCA PDCSNITWKG

    PVCGLDGKTY RNECALLKAR CKEQPELEVQ YQGRCKKTCR DVFCPGSSTC

    VVDQTNNAYC VTCNRICPEP ASSEQYLCGN DGVTYSSACH LRKATCLLGR

    SIGLAYEGKC IKAKSCEDIQ CTGGKKCLWD FKVGRGRCSL CDELCPDSKS

    DEPVCASDNA TYASECAMKE AACSSGVLLE VKHSGSCN


    Reactivity: Determined by its ability to neutralize Activin A inhibitory effect of murine MPC-11 cells. The expected ED50 us 0.1-0.4ug/ml in the presence of 7.5ng/ml Activin A.



    Precautions: For In vitro research Use Only. Not for use in or on humans or animals or for diagnostics. It is the responsibility of the user to comply with all local/state and Federal rules in the use of this product. We are not responsible for any patent infringements that might result with the use of or derivation of this product.

    (Note: I removed any references to prices)
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    Admin @ http://www.extrememuscle.co.nr - Come check out my board if ya get a chance!



  • #2
    I know this is reletively new so I don't think there would be too much info regarding dosage use. It's also an expensive compound.

    I'm wondering if injected would it only bind to myostatin around where it was originally injected or would it be carried into the blood stream to be distributed into other skeletal muscle.
    Bigger, Faster, Stronger

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    • #3
      So far I have not seen anything related to BBing as of yet:

      In early development of Xenopus laevis, it is known that activities of polypeptide growth factors are negatively regulated by their binding proteins. In this study, follistatin, originally known as an activin-binding protein, was shown to inhibit all aspects of bone morphogenetic protein (BMP) activity in early Xenopus embryos. Furthermore, using a surface plasmon resonance biosensor, we demonstrated that follistatin can directly interact with multiple BMPs at significantly high affinities. Interestingly, follistatin was found to be noncompetitive with the BMP receptor for ligand binding and to form a trimeric complex with BMP and its receptor. The results suggest that follistatin acts as an organizer factor in early amphibian embryogenesis by inhibiting BMP activities by a different mechanism from that used by chordin and noggin...
      "That damn log book"

      www.trueprotein.com Highest quality protein at the lowest price...

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      • #4
        I thought this was very interesting about BMP:

        For years, scientists have been searching for ways to stimulate the human body to generate and repair bone more reliably and more quickly. No one appreciates the importance of such research more than the spinal surgeon. More than half of the thousands of bone fusion operations performed annually in the United States involve fusion of the spinal column. Traditionally, spinal fusion requires the transplant of bone chips from a patient's pelvis to the spinal vertebrae to help "fuse" them together. Although this procedure can be very effective for the treatment of certain spinal disorders, the bone transplantation procedure (bone grafting) can prolong surgery, increase blood loss, increase hospital stay, increase recovery time, and increase recovery pain. Moreover, the bone grafting technique does not always reliably result in successful fusion of the vertebrae because of occasional inadequate bone growth.

        Recently, scientists and spinal surgeons have demonstrated that a genetically produced protein, recombinant human bone morphogenetic protein-2, or rhBMP-2, has the ability to stimulate a patient's own cells to make more bone. This finding has obvious beneficial implications for the treatment of many bone fractures and bone defects. More importantly, though, rhBMP-2 can be tremendously beneficial to patients undergoing spinal fusion. It will eliminate the need for bone transplantation from the pelvis. It may more reliably and more quickly produce fusion of spinal vertebrae. It may even reduce the need for the implantation of spinal rods and screws.

        The process of stimulating bone growth within the body is known as osteoinduction. One of the pioneers in the science of osteoinduction was Dr. Marshall Urist, Professor Emeritus of the Department of Orthopaedic Surgery at the UCLA School of Medicine. More than 35 years ago, Dr. Urist discovered that the proteins that directed bone to heal itself were contained within its own matrix, or substance. It was not until 1988 that these proteins were individually identified and genetically reproduced. Thereafter, it was quickly discovered that rhBMP-2 could, by itself, direct the repair and regeneration of bone in various parts of the skeleton. In several laboratory experiments performed from 1993 to 1997, rhBMP-2 was shown to effectively stimulate bone growth along spinal vertebrae.

        In 1997, rhBMP-2 was used for the first time in patients undergoing spinal fusion. In this initial clinical trial, all eleven patients who had been implanted with rhBMP-2 achieved successful fusion within 6 months from the time of surgery. In fact, 10 of these 11 patients had achieved their fusions within 3 months of surgery. Because these patients did not require bone grafting from the pelvis, their hospital stays were shorter and their post-surgical pain was less than typically seen with traditional bone grafting techniques. These promising initial findings are now being studied in several larger clinical trials throughout the United States.

        There is little doubt that powerful biologic proteins such as rhBMP-2 will eventually help all surgical specialists treat a variety of common as well as complex spinal disorders. These osteoinductive factors will enable surgeons to modify their techniques to minimize the invasiveness of their operations. Ultimately, the goal will be to reduce the pain associated with surgery and recovery, improve the effectiveness of the surgical treatments, and hasten the return of patients to productive and healthy lifestyles...
        "That damn log book"

        www.trueprotein.com Highest quality protein at the lowest price...

        Comment


        • #5
          I did a post on this on Animals board about 2 years back but there was a potential problem with follistatin usage (and i cant remember now why)--Ill look for it
          @dante_trudel

          Comment


          • #6
            Originally posted by Doggcrapp
            I did a post on this on Animals board about 2 years back but there was a potential problem with follistatin usage (and i cant remember now why)--Ill look for it

            Dante, Was it a problem with FSH?..
            "That damn log book"

            www.trueprotein.com Highest quality protein at the lowest price...

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            • #7
              follistatin binds to most of the tgfb's...it causes problems with controlling cell-division and other functions that the other tgfb's provide
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              • #8
                Regulation of Myostatin in Vivo by Growth and Differentiation Factor-Associated Serum Protein-1: A Novel Protein with Protease Inhibitor and Follistatin Domains
                Jennifer J. Hill, Yongchang Qiu, Rodney M. Hewick and Neil M. Wolfman
                Department of Protein Chemistry and Proteomics (J.J.H., Y.Q., R.M.H.), and Department of Musculoskeletal Sciences (N.M.W.), Wyeth Research, Cambridge, Massachusetts 02140

                Address all correspondence and requests for reprints to: Jennifer J. Hill, Department of Protein Chemistry and Proteomics, Wyeth Research, 200 Cambridge Park Drive, Cambridge, Massachusetts 02140. E-mail: [email protected].


                Myostatin, a member of the TGFß superfamily, is a potent and specific negative regulator of skeletal muscle mass. In serum, myostatin circulates as part of a latent complex containing myostatin propeptide and/or follistatin-related gene (FLRG). Here, we report the identification of an additional protein associated with endogenous myostatin in normal mouse and human serum, discovered by affinity purification and mass spectrometry. This protein, which we have named growth and differentiation factor-associated serum protein-1 (GASP-1), contains multiple domains associated with protease-inhibitory proteins, including a whey acidic protein domain, a Kazal domain, two Kunitz domains, and a netrin domain. GASP-1 also contains a domain homologous to the 10-cysteine repeat found in follistatin, a protein that binds and inhibits activin, another member of the TGFß superfamily. We have cloned mouse GASP-1 and shown that it inhibits the biological activity of mature myostatin, but not activin, in a luciferase reporter gene assay. Surprisingly, recombinant GASP-1 binds directly not only to mature myostatin, but also to the myostatin propeptide. Thus, GASP-1 represents a novel class of inhibitory TGFß binding proteins.


                Differential Response to Exogenous and Endogenous Myostatin in Myoblasts Suggests that Myostatin Acts as an Autocrine Factor in Vivo
                Ramón Ríos1, Susana Fernández-Nocelos, Isabel Carneiro, Víctor M. Arce and Jesús Devesa
                Departamento de Fisioloxía, Facultade de Medicina, Universidade de Santiago de Compostela, A Coruña 15782, Spain

                Address all correspondence and requests for reprints to: Víctor M. Arce, M.D., Ph.D., Departamento de Fisioloxía, Facultade de Medicina, Universidade de Santiago de Compostela, San Francisco 1, 15782 Santiago de Compostela, Spain. E-mail: [email protected].


                Myostatin is a member of the TGF-ß superfamily that is essential for proper regulation of skeletal muscle growth. As do other TGF-ß superfamily members, myostatin signals into the cell via a receptor complex that consists of two distinct transmembrane proteins, known as the type I and type II receptors. Vertebrates have seven distinct type I receptors, each of which can mix and match with one of five type I receptors to mediate signals for all the TGF-ß family ligands. Accumulating evidence indicates that myostatin shares its pair of receptors with activin, and therefore, the question arises about how specificity in signaling is achieved. Our hypothesis is that a mechanism has to exist to restrict myostatin actions to the muscle cells. To investigate this possibility, we compared the effect of endogenous myostatin (myostatin overexpressed by myoblasts) and exogenous myostatin (recombinant myostatin added to the culture medium) in cultured myoblasts. As opposed to exogenous myostatin, endogenous myostatin induced the transcription of a reporter vector in cultured myoblasts. Notably, the myostatin concentrations that failed to induce a response in myoblasts were effective in MCF-7 cells (human mammary carcinoma) and in HepG2 cells (human hepatic carcinoma). Based on our observations, we propose that a mechanism exists that differentially regulates the bioavailability of endogenous and exogenous myostatin to muscle cells. This is consistent with a model in which myostatin actions are exerted in vivo in an autocrine fashion

                Activation of latent myostatin by the BMP-1/tolloid family of metalloproteinases
                Neil M. Wolfman * , Alexandra C. McPherron , William N. Pappano ¶, Monique V. Davies ||, Kening Song **, Kathleen N. Tomkinson *, Jill F. Wright *, Liz Zhao **, Suzanne M. Sebald , Daniel S. Greenspan ¶ and Se-Jin Lee

                *Department of Inflammation, ||Antibody Technology Group, and **Department of Cardiovascular and Metabolic Diseases, Wyeth Research, 200 CambridgePark Drive, Cambridge, MA 02140; Department of Molecular Biology and Genetics, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205; and Departments of ¶Biomolecular Chemistry and Pathology and Laboratory Medicine, University of Wisconsin Medical School, 1300 University Avenue, Madison, WI 53706

                Edited by Eric N. Olson, University of Texas Southwestern Medical Center, Dallas, TX and approved October 6, 2003 (received for review August 4, 2003)



                Myostatin is a transforming growth factor family member that acts as a negative regulator of skeletal muscle growth. Myostatin circulates in the blood of adult mice in a noncovalently held complex with other proteins, including its propeptide, which maintain the C-terminal dimer in a latent, inactive state. This latent form of myostatin can be activated in vitro by treatment with acid; however, the mechanisms by which latent myostatin is activated in vivo are unknown. Here, we show that members of the bone morphogenetic protein-1/tolloid (BMP-1/TLD) family of metalloproteinases can cleave the myostatin propeptide in this complex and can thereby activate latent myostatin. Furthermore, we show that a mutant form of the propeptide resistant to cleavage by BMP-1/TLD proteinases can cause significant increases in muscle mass when injected into adult mice. These findings raise the possibility that members of the BMP-1/TLD family may be involved in activating latent myostatin in vivo and that molecules capable of inhibiting these proteinases may be effective agents for increasing muscle mass for both human therapeutic and agricultural applications.
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