ArticleAmerican journal of physiology. Cell physiology2010
Sphingomyelinase stimulates oxidant signaling to weaken skeletal muscle and promote fatigue.
Article in American journal of physiology. Cell physiology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 53 citations in OpenAlex.
- Deciphering the circulating lipidome signature associated with physical performance in gastric cancer patients: an exploratory study.Metabolomics : Official journal of the Metabolomic Society · 2026Article
- Two novel cases of biallelic SMPD4 variants with brain structural abnormalities.Neurogenetics · 2024Review
- Dynapenic Abdominal Obesity as a Risk Factor for Metabolic Syndrome in Individual 50 Years of Age or Older: English Longitudinal Study of Ageing.The journal of nutrition, health & aging · 2023Article
- Sphingomyelinase activity promotes atrophy and attenuates force in human muscle fibres and is elevated in heart failure patients.Journal of cachexia, sarcopenia and muscle · 2022Article
- Review
- Abnormal skeletal muscle blood flow, contractile mechanics and fibre morphology in a rat model of obese-HFpEF.The Journal of physiology · 2021Article
- Influence of Obesity and Type 2 Diabetes on Calcium Handling by Skeletal Muscle: Spotlight on the Sarcoplasmic Reticulum and Mitochondria.Frontiers in physiology · 2021Review
- Keep Your Friends Close, but Your Enemies Closer: Role of Acid Sphingomyelinase During Infection and Host Response.Frontiers in medicine · 2020Review
- The Emerging Roles of Nicotinamide Adenine Dinucleotide Phosphate Oxidase 2 in Skeletal Muscle Redox Signaling and Metabolism.Antioxidants & redox signaling · 2019Review
- Skeletal myofiber VEGF deficiency leads to mitochondrial, structural, and contractile alterations in mouse diaphragm.Journal of applied physiology (Bethesda, Md. : 1985) · 2019Article
- Small-hairpin RNA and pharmacological targeting of neutral sphingomyelinase prevent diaphragm weakness in rats with heart failure and reduced ejection fraction.American journal of physiology. Lung cellular and molecular physiology · 2019Article
- Mitochondria as a Target for Mitigating Sarcopenia.Frontiers in physiology · 2018Review
- Diaphragm abnormalities in heart failure and aging: mechanisms and integration of cardiovascular and respiratory pathophysiology.Heart failure reviews · 2017Review
- Disease-Induced Skeletal Muscle Atrophy and Fatigue.Medicine and science in sports and exercise · 2016Review
- Article
- Neutral sphingomyelinase 2 is required for cytokine-induced skeletal muscle calpain activation.American journal of physiology. Lung cellular and molecular physiology · 2015Article
- Diaphragm dysfunction caused by sphingomyelinase requires the p47(phox) subunit of NADPH oxidase.Respiratory physiology & neurobiology · 2015Article
- Diaphragm muscle weakness in mice is early-onset post-myocardial infarction and associated with elevated protein oxidation.Journal of applied physiology (Bethesda, Md. : 1985) · 2015Article
- Diaphragm dysfunction in heart failure is accompanied by increases in neutral sphingomyelinase activity and ceramide content.European journal of heart failure · 2014Article
- HDAC1 activates FoxO and is both sufficient and required for skeletal muscle atrophy.Journal of cell science · 2014Article
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Authors and funding
6 authors at 1 institution in 1 country.
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Abstract
Sphingomyelinase (SMase) hydrolyzes membrane sphingomyelin into ceramide, which increases oxidants in nonmuscle cells. Serum SMase activity is elevated in sepsis and heart failure, conditions where muscle oxidants are increased, maximal muscle force is diminished, and fatigue is accelerated. We tested the hypotheses that exogenous SMase and accumulation of ceramide in muscle increases oxidants in muscle cells, depresses specific force of unfatigued muscle, and accelerates the fatigue process. We also anticipated that the antioxidant N-acetylcysteine (NAC) would prevent SMase effects on muscle function. We studied the responses of C2C12 myotubes and mouse diaphragm to SMase treatment in vitro. We observed that SMase caused a 2.8-fold increase in total ceramide levels in myotubes. Exogenous ceramide and SMase elevated oxidant activity in C2C12 myotubes by 15-35% (P < 0.05) and in diaphragm muscle fiber bundles by 58-120% (P < 0.05). The SMase-induced increase in diaphragm oxidant activity was prevented by NAC. Exogenous ceramide depressed diaphragm force by 55% (P < 0.05), while SMase depressed maximal force by 30% (P < 0.05) and accelerated fatigue--effects opposed by treatment with NAC. In conclusion, our findings suggest that SMase stimulates a ceramide-oxidant signaling pathway that results in muscle weakness and fatigue.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.