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Nuclear factor-kappa B signaling in skeletal muscle atrophy

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Abstract

Skeletal muscle atrophy/wasting is a serious complication of a wide range of diseases and conditions such as aging, disuse, AIDS, chronic obstructive pulmonary disease, space travel, muscular dystrophy, chronic heart failure, sepsis, and cancer. Emerging evidence suggests that nuclear factor-kappa B (NF-κB) is one of the most important signaling pathways linked to the loss of skeletal muscle mass in various physiological and pathophysiological conditions. Activation of NF-κB in skeletal muscle leads to degradation of specific muscle proteins, induces inflammation and fibrosis, and blocks the regeneration of myofibers after injury/atrophy. Recent studies employing genetic mouse models have provided strong evidence that NF-κB can serve as an important molecular target for the prevention of skeletal muscle loss. In this article, we have outlined the current understanding regarding the role of NF-κB in skeletal muscle with particular reference to different models of muscle wasting and the development of novel therapy.

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Abbreviations

AP-1:

activator protein-1

CHF:

chronic heart failure

COPD:

chronic obstructive pulmonary disorder

DMD:

Duchenne muscular dystrophy

IFN:

interferon

IGF:

insulin growth factor

IkB:

I kappa B

IKK:

IkB kinase

IL:

interleukin

LGMD2A:

limb-girdle muscular dystrophy type 2A

LLC:

Lewis lung carcinoma

MMP:

matrix metalloproteinase

MuRF1:

muscle RING finger protein 1

NF-κB:

nuclear factor-kappa B

NIK:

NF-κB-inducing kinase

iNOS:

inducible nitric oxide synthase

PDTC:

pyrrolidine dithiocarbamate

PIF:

proteolysis-inducing factor

TNF:

tumor necrosis factor

TWEAK:

TNF-related weak inducer of apoptosis

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Acknowledgments

We would like to apologize to the many researchers whose contributions were not cited due to our oversight or space limitation. This work was supported by RO1 grant AG029623 from National Institute of Health (to AK).

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  1. Department of Anatomical Sciences and Neurobiology, University of Louisville School of Medicine, 500 South Preston Street, Louisville, KY, 40202, USA

    Hong Li, Shweta Malhotra & Ashok Kumar

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  1. Hong Li
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Correspondence to Ashok Kumar.

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Li, H., Malhotra, S. & Kumar, A. Nuclear factor-kappa B signaling in skeletal muscle atrophy. J Mol Med 86, 1113–1126 (2008). https://doi.org/10.1007/s00109-008-0373-8

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  • DOI: https://doi.org/10.1007/s00109-008-0373-8

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