ArticleRedox biology2014
Neutral sphingomyelinase-3 mediates TNF-stimulated oxidant activity in skeletal muscle.
Article in Redox biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 43 citations in OpenAlex.
- Repurposed Nrf2 activator dimethyl fumarate rescues muscle inflammation and fibrosis in an aggravated mdx mouse model of Duchenne muscular dystrophy.Redox biology · 2025Article
- High expression of SMPD4 promotes liver cancer and is associated with poor prognosis.BMC research notes · 2025Article
- Neutral sphingomyelinase 2: A promising drug target for CNS disease.Advances in pharmacology (San Diego, Calif.) · 2025Review
- Neutral sphingomyelinase regulates mechanotransduction in human engineered cardiac tissues and mouse hearts.The Journal of physiology · 2024Article
- Two novel cases of biallelic SMPD4 variants with brain structural abnormalities.Neurogenetics · 2024Review
- SMPD4 regulates mitotic nuclear envelope dynamics and its loss causes microcephaly and diabetes.Brain : a journal of neurology · 2023Article
- mNature metabolism · 2023Article
- Cross-Regulation of the Cellular Redox System, Oxygen, and Sphingolipid Signalling.Metabolites · 2023Review
- Vascular Smooth Muscle Cell Neutral Sphingomyelinase 2 in the Release of Exosomes and Vascular Calcification.International journal of molecular sciences · 2022Review
- Dysregulation of multiple signaling pathways: A possible cause of cerebral palsy.Experimental biology and medicine (Maywood, N.J.) · 2022Review
- CaNature communications · 2022Article
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- Probing compartment-specific sphingolipids with targeted bacterial sphingomyelinases and ceramidases.Journal of lipid research · 2019Article
- Loss of SMPD4 Causes a Developmental Disorder Characterized by Microcephaly and Congenital Arthrogryposis.American journal of human genetics · 2019Article
- Changes in Membrane Ceramide Pools in Rat Soleus Muscle in Response to Short-Term Disuse.International journal of molecular sciences · 2019Article
- Palmitoylation is required for TNF-R1 signaling.Cell communication and signaling : CCS · 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
- Patients experiencing statin-induced myalgia exhibit a unique program of skeletal muscle gene expression following statin re-challenge.PloS one · 2017Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
aimsSphingolipid and oxidant signaling affect glucose uptake, atrophy, and force production of skeletal muscle similarly and both are stimulated by tumor necrosis factor (TNF), suggesting a connection between systems. Sphingolipid signaling is initiated by neutral sphingomyelinase (nSMase), a family of agonist-activated effector enzymes. Northern blot analyses suggest that nSMase3 may be a striated muscle-specific nSMase. The present study tested the hypothesis that nSMase3 protein is expressed in skeletal muscle and functions to regulate TNF-stimulated oxidant production.
resultsWe demonstrate constitutive nSMase activity in skeletal muscles of healthy mice and humans and in differentiated C2C12 myotubes. nSMase3 (Smpd4 gene) mRNA is highly expressed in muscle. An nSMase3 protein doublet (88 and 85 kD) is derived from alternative mRNA splicing of exon 11. The proteins partition differently. The full-length 88 kD isoform (nSMase3a) fractionates with membrane proteins that are resistant to detergent extraction; the 85 kD isoform lacking exon 11 (nSMase3b) is more readily extracted and fractionates with detergent soluble membrane proteins; neither variant is detected in the cytosol. By immunofluorescence microscopy, nSMase3 resides in both internal and sarcolemmal membranes. Finally, myotube nSMase activity and cytosolic oxidant activity are stimulated by TNF. Both if these responses are inhibited by nSMase3 knockdown. INNOVATION: These findings identify nSMase3 as an intermediate that links TNF receptor activation, sphingolipid signaling, and skeletal muscle oxidant production.
conclusionOur data show that nSMase3 acts as a signaling nSMase in skeletal muscle that is essential for TNF-stimulated oxidant activity.
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Registered trials
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.