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Effect of spermine oxidase and p21 overexpression on skeletal muscle mRNA expression.

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE63008 | GEO | 2014/12/04

SECONDARY ACCESSION(S): PRJNA266415

REPOSITORIES: GEO

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Effect of spermine oxidase and p21 overexpression on skeletal muscle mRNA expression.

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2014-12-04 | E-GEOD-63008 | biostudies-arrayexpress

Effect of spermine oxidase overexpression on skeletal muscle mRNA expression.

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Effect of spermine oxidase overexpression on skeletal muscle mRNA expression.

Project description:For additional details see Bongers et al, Spermine Oxidase Maintains Basal Skeletal Muscle Gene Expression and Fiber Size, and Is Strongly Repressed by Conditions that Cause Skeletal Muscle Atrophy . Am J Physiol Endocrinol Metab. 2014 [under review] Bilateral tibialis anterior muscles of C57BL/6 mice were harvested seven days after transfection with spermine oxidase or control plasmid.

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Spermine oxidase maintains basal skeletal muscle gene expression and fiber size and is strongly repressed by conditions that cause skeletal muscle atrophy.

Project description:Skeletal muscle atrophy is a common and debilitating condition that remains poorly understood at the molecular level. To better understand the mechanisms of muscle atrophy, we used mouse models to search for a skeletal muscle protein that helps to maintain muscle mass and is specifically lost during muscle atrophy. We discovered that diverse causes of muscle atrophy (limb immobilization, fasting, muscle denervation, and aging) strongly reduced expression of the enzyme spermine oxidase. Importantly, a reduction in spermine oxidase was sufficient to induce muscle fiber atrophy. Conversely, forced expression of spermine oxidase increased muscle fiber size in multiple models of muscle atrophy (immobilization, fasting, and denervation). Interestingly, the reduction of spermine oxidase during muscle atrophy was mediated by p21, a protein that is highly induced during muscle atrophy and actively promotes muscle atrophy. In addition, we found that spermine oxidase decreased skeletal muscle mRNAs that promote muscle atrophy (e.g., myogenin) and increased mRNAs that help to maintain muscle mass (e.g., mitofusin-2). Thus, in healthy skeletal muscle, a relatively low level of p21 permits expression of spermine oxidase, which helps to maintain basal muscle gene expression and fiber size; conversely, during conditions that cause muscle atrophy, p21 expression rises, leading to reduced spermine oxidase expression, disruption of basal muscle gene expression, and muscle fiber atrophy. Collectively, these results identify spermine oxidase as an important positive regulator of muscle gene expression and fiber size, and elucidate p21-mediated repression of spermine oxidase as a key step in the pathogenesis of skeletal muscle atrophy.

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Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

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