ArticleMolecular pharmacology2008
Regulation of neutral sphingomyelinase-2 (nSMase2) by tumor necrosis factor-alpha involves protein kinase C-delta in lung epithelial cells.
Article in Molecular pharmacology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 73 citations in OpenAlex.
- Hepatic sphingomyelin phosphodiesterase 3 promotes steatohepatitis by disrupting membrane sphingolipid metabolism.Cell metabolism · 2025Article
- Neutral sphingomyelinase 2: A promising drug target for CNS disease.Advances in pharmacology (San Diego, Calif.) · 2025Review
- Vasodilator reactive oxygen species ameliorate perturbed myocardial oxygen delivery in exercising swine with multiple comorbidities.Basic research in cardiology · 2024Article
- Serotonin Signaling through Lipid Membranes.ACS chemical neuroscience · 2024Review
- Dynamic changes in the proximitome of neutral sphingomyelinase-2 (nSMase2) in TNFα stimulated Jurkat cells.Frontiers in immunology · 2024Article
- The Lard Works in Mysterious Ways: Ceramides in Nutrition-Linked Chronic Disease.Annual review of nutrition · 2022Review
- Inhibition of neutral sphingomyelinase 2 reduces extracellular vesicle release from neurons, oligodendrocytes, and activated microglial cells following acute brain injury.Biochemical pharmacology · 2021Article
- Neutral sphingomyelinase-2 and cardiometabolic diseases.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2021Review
- A Comprehensive Review: Sphingolipid Metabolism and Implications of Disruption in Sphingolipid Homeostasis.International journal of molecular sciences · 2021Review
- Review
- Neutral sphingomyelinase 2 regulates inflammatory responses in monocytes/macrophages induced by TNF-α.Scientific reports · 2020Article
- Sphingolipids in COPD.European respiratory review : an official journal of the European Respiratory Society · 2019Review
- Beneficial role of bioactive lipids in the pathobiology, prevention, and management of HBV, HCV and alcoholic hepatitis, NAFLD, and liver cirrhosis: A review.Journal of advanced research · 2019Review
- Mechanism of Rapid Nuclear Factor-E2-Related Factor 2 (Nrf2) Activation via Membrane-Associated Estrogen Receptors: Roles of NADPH Oxidase 1, Neutral Sphingomyelinase 2 and Epidermal Growth Factor Receptor (EGFR).Antioxidants (Basel, Switzerland) · 2019Review
- Sphingomyelin Breakdown in T Cells: Role of Membrane Compartmentalization in T Cell Signaling and Interference by a Pathogen.Frontiers in cell and developmental biology · 2019Review
- Sphingolipids in neurodegeneration (with focus on ceramide and S1P).Advances in biological regulation · 2018Review
- Enriched Expression of Neutral Sphingomyelinase 2 in the Striatum is Essential for Regulation of Lipid Raft Content and Motor Coordination.Molecular neurobiology · 2018Article
- Arachidonic acid and other unsaturated fatty acids and some of their metabolites function as endogenous antimicrobial molecules: A review.Journal of advanced research · 2018Review
- Novel function of ceramide for regulation of mitochondrial ATP release in astrocytes.Journal of lipid research · 2018Article
- ATRA transcriptionally induces nSMase2 through CBP/p300-mediated histone acetylation.Journal of lipid research · 2016Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Neutral sphingomyelinases (N-SMases) are major candidates for stress-induced ceramide production, but there is still limited knowledge of the regulatory mechanisms of the cloned N-SMase enzyme-nSMase2. We have reported that p38 mitogen-activated protein kinase (MAPK) was upstream of nSMase2 in tumor necrosis-alpha (TNF-alpha)-stimulated A549 cells ( J Biol Chem 282: 1384-1396, 2007 ). Here, we report a role for protein kinase C (PKC) in mediating TNF-induced translocation of nSMase2 from the Golgi to the plasma membrane (PM). Pharmacological inhibition of PKCs prevented TNF-stimulated nSMase2 translocation to the PM in A549 cells. Using phorbol 12-myristate 13-acetate (PMA) as a tool to dissect PKC responses, we found that PMA induced nSMase2 translocation to the PM in a time- and dose-dependent manner. Pharmacological inhibitors and specific siRNA implicated the novel PKCs, specifically PKC-delta, in both TNF and PMA-stimulated nSMase2 translocation. However, PMA did not increase in vitro N-SMase activity and PKC-delta did not regulate TNF-induced N-SMase activity. Furthermore, PKC-delta and nSMase2 did not coimmunoprecipitate, suggesting that other signaling proteins may be involved. PMA-stimulated nSMase2 translocation was independent of p38 MAPK, and neither PKC inhibitors nor small interfering RNA had significant effects on TNF-stimulated p38 MAPK activation, indicating that PKC-delta does not act through p38 MAPK in regulating nSMase2. Finally, down-regulation of PKC-delta inhibited induction of vascular cell and intercellular adhesion molecules, previously identified as downstream of nSMase2 in A549 cells. Taken together, these data implicate PKC-delta as a regulator of nSMase2 and, for the first time, identify nSMase2 as a point of cross-talk between the PKC and sphingolipid pathways.
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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.