TY - JOUR
T1 - Regulation of muscle protein synthesis and the effects of catabolic states
AU - Gordon, Bradley S.
AU - Kelleher, Andrew R.
AU - Kimball, Scot R.
N1 - Funding Information:
The authors would like to thank Dr. Leonard S. Jefferson for critical reading and helpful comments during preparation of the manuscript. Work described in this document that was performed in the authors’ laboratory was supported by NIH grant DK15658 .
PY - 2013
Y1 - 2013
N2 - Protein synthesis and degradation are dynamically regulated processes that act in concert to control the accretion or loss of muscle mass. The present article focuses on the mechanisms involved in the impairment of protein synthesis that are associated with skeletal muscle atrophy. The vast majority of mechanisms known to regulate protein synthesis involve modulation of the initiation phase of mRNA translation, which comprises a series of reactions that result in the binding of initiator methionyl-tRNAi and mRNA to the 40S ribosomal subunit. The function of the proteins involved in both events has been shown to be repressed under atrophic conditions such as sepsis, cachexia, chronic kidney disease, sarcopenia, and disuse atrophy. The basis for the inhibition of protein synthesis under such conditions is likely to be multifactorial and includes insulin/insulin-like growth factor 1 resistance, pro-inflammatory cytokine expression, malnutrition, corticosteroids, and/or physical inactivity. The present article provides an overview of the existing literature regarding mechanisms and signaling pathways involved in the regulation of mRNA translation as they apply to skeletal muscle wasting, as well as the efficacy of potential clinical interventions such as nutrition and exercise in the maintenance of skeletal muscle protein synthesis under atrophic conditions. This article is part of a Directed Issue entitled: Molecular basis of muscle wasting.
AB - Protein synthesis and degradation are dynamically regulated processes that act in concert to control the accretion or loss of muscle mass. The present article focuses on the mechanisms involved in the impairment of protein synthesis that are associated with skeletal muscle atrophy. The vast majority of mechanisms known to regulate protein synthesis involve modulation of the initiation phase of mRNA translation, which comprises a series of reactions that result in the binding of initiator methionyl-tRNAi and mRNA to the 40S ribosomal subunit. The function of the proteins involved in both events has been shown to be repressed under atrophic conditions such as sepsis, cachexia, chronic kidney disease, sarcopenia, and disuse atrophy. The basis for the inhibition of protein synthesis under such conditions is likely to be multifactorial and includes insulin/insulin-like growth factor 1 resistance, pro-inflammatory cytokine expression, malnutrition, corticosteroids, and/or physical inactivity. The present article provides an overview of the existing literature regarding mechanisms and signaling pathways involved in the regulation of mRNA translation as they apply to skeletal muscle wasting, as well as the efficacy of potential clinical interventions such as nutrition and exercise in the maintenance of skeletal muscle protein synthesis under atrophic conditions. This article is part of a Directed Issue entitled: Molecular basis of muscle wasting.
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U2 - 10.1016/j.biocel.2013.05.039
DO - 10.1016/j.biocel.2013.05.039
M3 - Review article
C2 - 23769967
AN - SCOPUS:84885174843
SN - 1357-2725
VL - 45
SP - 2147
EP - 2157
JO - International Journal of Biochemistry and Cell Biology
JF - International Journal of Biochemistry and Cell Biology
IS - 10
ER -