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Med. Sci. 2018, 6(1), 14; https://doi.org/10.3390/medsci6010014

Skeletal Muscle Pathophysiology: The Emerging Role of Spermine Oxidase and Spermidine

1
Department of Science, Università degli Studi di Roma “Roma Tre”, 00146 Rome, Italy
2
Department of of Movement Human and Health Sciences, Unit of Biology, Genetics and Biochemistry, Università degli Studi di Roma “Foro Italico”, Piazza Lauro De Bosis 15, 00135 Rome, Italy
*
Author to whom correspondence should be addressed.
Received: 30 November 2017 / Revised: 7 February 2018 / Accepted: 9 February 2018 / Published: 14 February 2018
(This article belongs to the Special Issue Polyamine Metabolism in Disease and Polyamine-Targeted Therapies)
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Abstract

Skeletal muscle comprises approximately 40% of the total body mass. Preserving muscle health and function is essential for the entire body in order to counteract chronic diseases such as type II diabetes, cardiovascular diseases, and cancer. Prolonged physical inactivity, particularly among the elderly, causes muscle atrophy, a pathological state with adverse outcomes such as poor quality of life, physical disability, and high mortality. In murine skeletal muscle C2C12 cells, increased expression of the spermine oxidase (SMOX) enzyme has been found during cell differentiation. Notably, SMOX overexpression increases muscle fiber size, while SMOX reduction was enough to induce muscle atrophy in multiple murine models. Of note, the SMOX reaction product spermidine appears to be involved in skeletal muscle atrophy/hypertrophy. It is effective in reactivating autophagy, ameliorating the myopathic defects of collagen VI-null mice. Moreover, spermidine treatment, if combined with exercise, can affect D-gal-induced aging-related skeletal muscle atrophy. This review hypothesizes a role for SMOX during skeletal muscle differentiation and outlines its role and that of spermidine in muscle atrophy. The identification of new molecular pathways involved in the maintenance of skeletal muscle health could be beneficial in developing novel therapeutic lead compounds to treat muscle atrophy. View Full-Text
Keywords: aging; atrophy; autophagy; oxidative stress; polyamines; skeletal muscle; spermidine; spermine oxidase; transgenic mouse aging; atrophy; autophagy; oxidative stress; polyamines; skeletal muscle; spermidine; spermine oxidase; transgenic mouse
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Cervelli, M.; Leonetti, A.; Duranti, G.; Sabatini, S.; Ceci, R.; Mariottini, P. Skeletal Muscle Pathophysiology: The Emerging Role of Spermine Oxidase and Spermidine. Med. Sci. 2018, 6, 14.

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