ArticleAmerican journal of physiology. Endocrinology and metabolism2015
Spermine oxidase maintains basal skeletal muscle gene expression and fiber size and is strongly repressed by conditions that cause skeletal muscle atrophy.
Article in American journal of physiology. Endocrinology and metabolism, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 57 citations in OpenAlex.
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- Unfolding Resilience: Molecular Integration of the Integrated Stress Response and Mitochondrial UPR in Skeletal Muscle Homeostasis.Muscles (Basel, Switzerland) · 2026Review
- OGG1 increases exercise endurance via elevated skeletal muscle FGF21.The Journal of biological chemistry · 2026Article
- H-silicene nanosheets as a novel therapeutic approach for disuse muscle atrophy by modulating macrophage polarization.Materials today. Bio · 2025Article
- A Novel Research Paradigm for Sarcopenia of Limb Muscles: Lessons From the Perpetually Working Diaphragm's Anti-Aging Mechanisms.Journal of cachexia, sarcopenia and muscle · 2025Article
- Tumour-induced alterations in single-nucleus transcriptome of atrophying muscles indicate enhanced protein degradation and reduced oxidative metabolism.Journal of cachexia, sarcopenia and muscle · 2024Article
- Human myofiber-enriched aging-induced lncRNA FRAIL1 promotes loss of skeletal muscle function.Aging cell · 2024Article
- The mitochondrial ATP-dependent potassium channel (mitoKCell death & disease · 2024Article
- Distinct longevity mechanisms across and within species and their association with aging.Cell · 2023Article
- Genome-Wide Association Analysis Identifies Genomic Regions and Candidate Genes for Growth and Fatness Traits in Diannan Small-Ear (DSE) Pigs.Animals : an open access journal from MDPI · 2023Article
- Spermine oxidase induces DNA damage and sensitizes fusion negative rhabdomyosarcoma cells to irradiation.Frontiers in cell and developmental biology · 2023Article
- Identification of Metabolic Signature Associated with Idiopathic Inflammatory Myopathy Reveals Polyamine Pathway Alteration in Muscle Tissue.Metabolites · 2022Article
- The Impact of Spermidine on C2C12 Myoblasts Proliferation, Redox Status and Polyamines Metabolism under HInternational journal of molecular sciences · 2022Article
- Biology of Activating Transcription Factor 4 (ATF4) and Its Role in Skeletal Muscle Atrophy.The Journal of nutrition · 2022Review
- Identification of differentially expressed genes in mouse paraspinal muscle in response to microgravity.Frontiers in endocrinology · 2022Article
- Colorectal Cancer Chemotherapy Drug Bevacizumab May Induce Muscle Atrophy Through CDKN1A and TIMP4.Frontiers in oncology · 2022Article
- Sex differences in metabolic pathways are regulated by Pfkfb3 and Pdk4 expression in rodent muscle.Communications biology · 2021Article
- An Analysis of Differentially Expressed Coding and Long Non-Coding RNAs in Multiple Models of Skeletal Muscle Atrophy.International journal of molecular sciences · 2021Article
- Spinal motor neuron loss occurs through a p53-and-p21-independent mechanism in the SmnExperimental neurology · 2021Article
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
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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