Mechanisms involved in the enhancement of mammalian target of rapamycin signalling and hypertrophy in skeletal muscle of myostatin-deficient mice

Christopher Lipina, Hannah Kendall, Alexandra C. McPherron, Peter M. Taylor, Harinder S. Hundal

    Research output: Contribution to journalArticle

    47 Citations (Scopus)

    Abstract

    Myostatin deficiency leads to both an increased rate of protein synthesis and skeletal muscle hypertrophy. However, the mechanisms involved in mediating these effects are not yet fully understood. Here, we demonstrate that genetic loss of myostatin leads to enhanced muscle expression of both protein kinase B and mammalian target of rapamycin/S6K signalling components, consistent with their elevated activity. This is associated with a reduction in the expression of PGC1 alpha and COX IV, proteins which play important roles in maintaining mitochondrial function. Furthermore, we show that these changes in signalling and protein expression are largely independent of alterations in intramuscular amino acid content. Our findings, therefore, reveal potential new mechanisms and further contribute to our understanding of myostatin-regulated skeletal muscle growth and function. (C) 2010 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.

    Original languageEnglish
    Pages (from-to)2403-2408
    Number of pages6
    JournalFEBS Letters
    Volume584
    Issue number11
    DOIs
    Publication statusPublished - 3 Jun 2010

    Keywords

    • Growth differentiation factor-8
    • mTOR
    • p70S6K1
    • PKB/Akt
    • PROTEIN-KINASE-B
    • MYOBLAST DIFFERENTIATION
    • MYOTUBE HYPERTROPHY
    • INSULIN SENSITIVITY
    • WEIGHT-LOSS
    • IGF-I
    • EXPRESSION
    • AKT
    • PHOSPHORYLATION
    • RESISTANCE

    Cite this

    @article{11aca99053964cd7a05e3d506a9b4925,
    title = "Mechanisms involved in the enhancement of mammalian target of rapamycin signalling and hypertrophy in skeletal muscle of myostatin-deficient mice",
    abstract = "Myostatin deficiency leads to both an increased rate of protein synthesis and skeletal muscle hypertrophy. However, the mechanisms involved in mediating these effects are not yet fully understood. Here, we demonstrate that genetic loss of myostatin leads to enhanced muscle expression of both protein kinase B and mammalian target of rapamycin/S6K signalling components, consistent with their elevated activity. This is associated with a reduction in the expression of PGC1 alpha and COX IV, proteins which play important roles in maintaining mitochondrial function. Furthermore, we show that these changes in signalling and protein expression are largely independent of alterations in intramuscular amino acid content. Our findings, therefore, reveal potential new mechanisms and further contribute to our understanding of myostatin-regulated skeletal muscle growth and function. (C) 2010 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.",
    keywords = "Growth differentiation factor-8, mTOR, p70S6K1, PKB/Akt, PROTEIN-KINASE-B, MYOBLAST DIFFERENTIATION, MYOTUBE HYPERTROPHY, INSULIN SENSITIVITY, WEIGHT-LOSS, IGF-I, EXPRESSION, AKT, PHOSPHORYLATION, RESISTANCE",
    author = "Christopher Lipina and Hannah Kendall and McPherron, {Alexandra C.} and Taylor, {Peter M.} and Hundal, {Harinder S.}",
    year = "2010",
    month = "6",
    day = "3",
    doi = "10.1016/j.febslet.2010.04.039",
    language = "English",
    volume = "584",
    pages = "2403--2408",
    journal = "FEBS Letters",
    issn = "0014-5793",
    publisher = "Wiley",
    number = "11",

    }

    Mechanisms involved in the enhancement of mammalian target of rapamycin signalling and hypertrophy in skeletal muscle of myostatin-deficient mice. / Lipina, Christopher; Kendall, Hannah; McPherron, Alexandra C.; Taylor, Peter M.; Hundal, Harinder S.

    In: FEBS Letters, Vol. 584, No. 11, 03.06.2010, p. 2403-2408.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Mechanisms involved in the enhancement of mammalian target of rapamycin signalling and hypertrophy in skeletal muscle of myostatin-deficient mice

    AU - Lipina, Christopher

    AU - Kendall, Hannah

    AU - McPherron, Alexandra C.

    AU - Taylor, Peter M.

    AU - Hundal, Harinder S.

    PY - 2010/6/3

    Y1 - 2010/6/3

    N2 - Myostatin deficiency leads to both an increased rate of protein synthesis and skeletal muscle hypertrophy. However, the mechanisms involved in mediating these effects are not yet fully understood. Here, we demonstrate that genetic loss of myostatin leads to enhanced muscle expression of both protein kinase B and mammalian target of rapamycin/S6K signalling components, consistent with their elevated activity. This is associated with a reduction in the expression of PGC1 alpha and COX IV, proteins which play important roles in maintaining mitochondrial function. Furthermore, we show that these changes in signalling and protein expression are largely independent of alterations in intramuscular amino acid content. Our findings, therefore, reveal potential new mechanisms and further contribute to our understanding of myostatin-regulated skeletal muscle growth and function. (C) 2010 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.

    AB - Myostatin deficiency leads to both an increased rate of protein synthesis and skeletal muscle hypertrophy. However, the mechanisms involved in mediating these effects are not yet fully understood. Here, we demonstrate that genetic loss of myostatin leads to enhanced muscle expression of both protein kinase B and mammalian target of rapamycin/S6K signalling components, consistent with their elevated activity. This is associated with a reduction in the expression of PGC1 alpha and COX IV, proteins which play important roles in maintaining mitochondrial function. Furthermore, we show that these changes in signalling and protein expression are largely independent of alterations in intramuscular amino acid content. Our findings, therefore, reveal potential new mechanisms and further contribute to our understanding of myostatin-regulated skeletal muscle growth and function. (C) 2010 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.

    KW - Growth differentiation factor-8

    KW - mTOR

    KW - p70S6K1

    KW - PKB/Akt

    KW - PROTEIN-KINASE-B

    KW - MYOBLAST DIFFERENTIATION

    KW - MYOTUBE HYPERTROPHY

    KW - INSULIN SENSITIVITY

    KW - WEIGHT-LOSS

    KW - IGF-I

    KW - EXPRESSION

    KW - AKT

    KW - PHOSPHORYLATION

    KW - RESISTANCE

    U2 - 10.1016/j.febslet.2010.04.039

    DO - 10.1016/j.febslet.2010.04.039

    M3 - Article

    VL - 584

    SP - 2403

    EP - 2408

    JO - FEBS Letters

    JF - FEBS Letters

    SN - 0014-5793

    IS - 11

    ER -