ArticleThe Journal of biological chemistry2010
Studies on the role of acid sphingomyelinase and ceramide in the regulation of tumor necrosis factor alpha (TNFalpha)-converting enzyme activity and TNFalpha secretion in macrophages.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 59 citations in OpenAlex.
- Sphingolipids in Emotional Well-Being.Journal of neurochemistry · 2026Review
- Podocyte-specific acid sphingomyelinase overexpression promotes gasdermin D dependent pyroptosis by impairing autophagic flux during obesity.Frontiers in physiology · 2026Article
- Podocyte-specific silencing of acid sphingomyelinase gene to abrogate hyperhomocysteinemia-induced NLRP3 inflammasome activation and glomerular inflammation.American journal of physiology. Renal physiology · 2024Article
- Nutritional roles and therapeutic potentials of dietary sphingomyelin in brain diseases.Journal of clinical biochemistry and nutrition · 2024Article
- Acid sphingomyelinase as a pathological and therapeutic target in neurological disorders: focus on Alzheimer's disease.Experimental & molecular medicine · 2024Review
- Lipidomic assessment of the impact of Nannochloropsis oceanica microalga lipid extract on human skin keratinocytes exposed to chronic UVB radiation.Scientific reports · 2023Article
- Cannabidiol and Cannabigerol Modify the Composition and Physicochemical Properties of Keratinocyte Membranes Exposed to UVA.International journal of molecular sciences · 2023Article
- Adiponectin receptor agonist ameliorates cardiac lipotoxicity via enhancing ceramide metabolism in type 2 diabetic mice.Cell death & disease · 2022Article
- Utilizing Sphingomyelinase Sensitizing Liposomes in Imaging Intestinal Inflammation in Dextran Sulfate Sodium-Induced Murine Colitis.Biomedicines · 2022Article
- Article
- Effects of Natural Antioxidants on Phospholipid and Ceramide Profiles of 3D-Cultured Skin Fibroblasts Exposed to UVA or UVB Radiation.Antioxidants (Basel, Switzerland) · 2021Article
- Global and Simultaneous Hypothesis Testing for High-Dimensional Logistic Regression Models.Journal of the American Statistical Association · 2021Article
- A Novel Combination of Fruits and Vegetables Prevents Diet-Induced Hepatic Steatosis and Metabolic Dysfunction in Mice.The Journal of nutrition · 2020Article
- Potential therapeutic target for aging and age-related neurodegenerative diseases: the role of acid sphingomyelinase.Experimental & molecular medicine · 2020Review
- Review
- Acid sphingomyelinase mediates human CD4Cell death & disease · 2017Review
- Article
- Co-operation of TLR4 and raft proteins in LPS-induced pro-inflammatory signaling.Cellular and molecular life sciences : CMLS · 2015Review
- Defining a role for acid sphingomyelinase in the p38/interleukin-6 pathway.The Journal of biological chemistry · 2014Article
- Acid sphingomyelinase determines melanoma progression and metastatic behaviour via the microphtalmia-associated transcription factor signalling pathway.Cell death and differentiation · 2014Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Acid sphingomyelinase (ASMase) has been proposed to mediate lipopolysaccharide (LPS) signaling in various cell types. This study shows that ASMase is a negative regulator of LPS-induced tumor necrosis factor alpha (TNFalpha) secretion in macrophages. ASMase-deficient (asm(-/-)) mice and isolated peritoneal macrophages produce severalfold more TNFalpha than their wild-type (asm(+/+)) counterparts when stimulated with LPS, whereas the addition of exogenous ceramides or sphingomyelinase reduces the differences. The underlying mechanism for these effects is not transcriptional but post-translational. The TNFalpha-converting enzyme (TACE) catalyzes the maturation of the 26-kDa precursor (pro-TNFalpha) to an active 17-kDa form (soluble (s)TNFalpha). In mouse peritoneal macrophages, the activity of TACE was the rate-limiting factor regulating TNFalpha production. A substantial portion of the translated pro-TNFalpha was not processed to sTNFalpha; instead, it was rapidly internalized and degraded in the lysosomes. TACE activity was 2-3-fold higher in asm(-/-) macrophages as compared with asm(+/+) macrophages and was suppressed when cells were treated with exogenous ceramide and sphingomyelinase. Indirect immunofluorescence analyses revealed distinct TNFalpha-positive structures in the close vicinity of the plasma membrane in asm(-/-) but not in asm(+/+) macrophages. asm(-/-) cells also had a higher number of early endosomal antigen 1-positive early endosomes. Experiments that involved inhibitors of TACE, endocytosis, and lysosomal proteolysis suggest that in the asm(-/-) cells a significant portion of pro-TNFalpha was sequestered within the early endosomes, and instead of undergoing lysosomal proteolysis, it was recycled to the plasma membrane and processed to sTNFalpha.
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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.