ArticleAmerican journal of physiology. Lung cellular and molecular physiology2015
Neutral sphingomyelinase 2 is required for cytokine-induced skeletal muscle calpain activation.
Article in American journal of physiology. Lung cellular and molecular physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.
- Sarcopenia and cardiovascular diseases: A systematic review and meta-analysis.Journal of cachexia, sarcopenia and muscle · 2023Pooled it
- Nicotine Reprograms Aging-Related Metabolism and Protects Against Motor Decline in Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- β2-Adrenergic Regulation of the Neuromuscular Transmission and Its Lipid-Dependent Switch.Molecular neurobiology · 2024Article
- 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
- Mitoquinone mesylate (MitoQ) prevents sepsis-induced diaphragm dysfunction.Journal of applied physiology (Bethesda, Md. : 1985) · 2021Article
- Skeletal muscle-specific calpastatin overexpression mitigates muscle weakness in aging and extends life span.Journal of applied physiology (Bethesda, Md. : 1985) · 2021Article
- Nipping disease in the bud: nSMase2 inhibitors as therapeutics in extracellular vesicle-mediated diseases.Drug discovery today · 2021Review
- The nSMase2/Smpd3 gene modulates the severity of muscular dystrophy and the emotional stress response in mdx mice.BMC medicine · 2020Article
- MitoTEMPOL, a mitochondrial targeted antioxidant, prevents sepsis-induced diaphragm dysfunction.American journal of physiology. Lung cellular and molecular physiology · 2020Article
- SS31, a mitochondrially targeted antioxidant, prevents sepsis-induced reductions in diaphragm strength and endurance.Journal of applied physiology (Bethesda, Md. : 1985) · 2020Article
- Diaphragm weakness and proteomics (global and redox) modifications in heart failure with reduced ejection fraction in rats.Journal of molecular and cellular cardiology · 2020Article
- Taurine administration ablates sepsis induced diaphragm weakness.Respiratory physiology & neurobiology · 2020Article
- 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
- Diaphragm Dysfunction in Critical Illness.Chest · 2018Review
- Diaphragm abnormalities in heart failure and aging: mechanisms and integration of cardiovascular and respiratory pathophysiology.Heart failure reviews · 2017Review
- Calcium-dependent phospholipase A2 modulates infection-induced diaphragm dysfunction.American journal of physiology. Lung cellular and molecular physiology · 2016Article
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5 authors at 1 institution in 1 country.
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Abstract
Calpain contributes to infection-induced diaphragm dysfunction but the upstream mechanism(s) responsible for calpain activation are poorly understood. It is known, however, that cytokines activate neutral sphingomyelinase (nSMase) and nSMase has downstream effects with the potential to increase calpain activity. We tested the hypothesis that infection-induced skeletal muscle calpain activation is a consequence of nSMase activation. We administered cytomix (20 ng/ml TNF-α, 50 U/ml IL-1β, 100 U/ml IFN-γ, 10 μg/ml LPS) to C2C12 muscle cells to simulate the effects of infection in vitro and studied mice undergoing cecal ligation puncture (CLP) as an in vivo model of infection. In cell studies, we assessed sphingomyelinase activity, subcellular calcium levels, and calpain activity and determined the effects of inhibiting sphingomyelinase using chemical (GW4869) and genetic (siRNA to nSMase2 and nSMase3) techniques. We assessed diaphragm force and calpain activity and utilized GW4869 to inhibit sphingomyelinase in mice. Cytomix increased cytosolic and mitochondrial calcium levels in C2C12 cells (P < 0.001); addition of GW4869 blocked these increases (P < 0.001). Cytomix also activated calpain, increasing calpain activity (P < 0.02), and the calpain-mediated cleavage of procaspase 12 (P < 0.001). Procaspase 12 cleavage was attenuated by either GW4869 (P < 0.001), BAPTA-AM (P < 0.001), or siRNA to nSMase2 (P < 0.001) but was unaffected by siRNA to nSMase3. GW4869 prevented CLP-induced diaphragm calpain activation and diaphragm weakness in mice. These data suggest that nSMase2 activation is required for the development of infection-induced diaphragm calpain activation and muscle weakness. As a consequence, therapies that inhibit nSMase2 in patients may prevent infection-induced skeletal muscle dysfunction.
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