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Diabetes-induced atrophy is associated with a muscle-specific alteration in NF-κB activation and expression

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Cell Stress and Chaperones Aims and scope

Abstract

NF-κB is a transcription factor implicated in pathological responses that develop during diabetes mellitus, including skeletal muscle atrophy. Given that NF-κB activation, protein composition, and content within diabetic skeletal muscle remain generally uncharacterized, a streptozotocin (STZ) model was used to assess NF-κB activation, composition, and content. Sprague-Dawley rats were injected with STZ (55 mg/kg) and after 30 days the soleus (SOL), plantaris (PL), red gastrocnemius (RG), and white gastrocnemius (WG) muscles were assessed by electrophoresis mobility shift assay and western blotting. NF-κB activation was detected in all muscles examined, but was reduced in RG muscles from diabetic animals. Supershifts indicated NF-κB was composed primarily of p50 in diabetic and control animals. The content of both p65 and p52 was elevated in SOL and PL muscles, while p52 was decreased in RG. The coactivating protein, Bcl-3, was increased in WG and RG, but decreased in PL. Both p50 and RelB remained unchanged in all tissues examined. All muscles from diabetic animals demonstrated reduced mass when compared to controls, but only the gastrocnemius demonstrated atrophy as reflected by a reduced muscle-to-body mass ratio. In conclusion, diabetic alterations to the contents and activation of the NF-κB protein were tissue-specific, but did not appear to alter dimer composition of constitutively bound NF-κB. These results indicate that diabetes may alter NF-κB activity and expression in a muscle-specific manner.

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Authors and Affiliations

  1. School of Kinesiology, Faculty of Health Sciences, Research Institute, University of Western Ontario, London, ON, Canada

    Bruce C. Frier & Earl G. Noble

  2. Lawson Health, Research Institute, University of Western Ontario, London, ON, Canada

    Earl G. Noble

  3. Faculty of Physical Education and Health, University of Toronto, 55 Harbord Street, , Toronto, ON, M5S 2W6, Canada

    Marius Locke

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  1. Bruce C. Frier
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  2. Earl G. Noble
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  3. Marius Locke
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Correspondence to Marius Locke.

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Frier, B.C., Noble, E.G. & Locke, M. Diabetes-induced atrophy is associated with a muscle-specific alteration in NF-κB activation and expression. Cell Stress and Chaperones 13, 287–296 (2008). https://doi.org/10.1007/s12192-008-0062-0

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  • DOI: https://doi.org/10.1007/s12192-008-0062-0

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