ArticleThe Journal of biological chemistry2009
Acid beta-glucosidase 1 counteracts p38delta-dependent induction of interleukin-6: possible role for ceramide as an anti-inflammatory lipid.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 54 citations in OpenAlex.
- Sphingomyelin synthase 2 deficiency suppresses airway mucus accumulation by altering sphingolipid flux and mucin glycosylation.Molecular and cellular biochemistry · 2026Article
- Search for Potential VDR/Partner Composite Elements in Regulatory DNA of Genes Associated with Respiratory Infections and Atopic Diseases.International journal of molecular sciences · 2025Article
- Natural history of inflammation and impaired autophagy in children with Gaucher disease identified by newborn screening.Molecular genetics and metabolism reports · 2025Article
- The Role of Vitamin E Isoforms and Metabolites in Cancer Prevention: Mechanistic Insights into Sphingolipid Metabolism Modulation.Nutrients · 2024Review
- Sphingolipid-Induced Bone Regulation and Its Emerging Role in Dysfunction Due to Disease and Infection.International journal of molecular sciences · 2024Review
- Article
- GBA inhibition suppresses ovarian cancer growth, survival and receptor tyrosine kinase AXL-mediated signaling pathways.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2023Article
- Host-microbial co-metabolites modulated by human milk oligosaccharides relate to reduced risk of respiratory tract infections.Frontiers in nutrition · 2022Article
- Role of Sphingolipids in Multiple Myeloma Progression, Drug Resistance, and Their Potential as Therapeutic Targets.Frontiers in oncology · 2022Review
- Article
- A Special View of What Was Almost Forgotten: p38δ MAPK.Cancers · 2021Review
- Cross-talks among GBA mutations, glucocerebrosidase, and α-synuclein in GBA-associated Parkinson's disease and their targeted therapeutic approaches: a comprehensive review.Translational neurodegeneration · 2021Review
- Review
- Multi-hierarchical profiling the structure-activity relationships of engineered nanomaterials at nano-bio interfaces.Nature communications · 2018Article
- Identification of an acid sphingomyelinase ceramide kinase pathway in the regulation of the chemokine CCL5.Journal of lipid research · 2018Article
- GBA-Associated Parkinson's Disease and Other Synucleinopathies.Current neurology and neuroscience reports · 2018Review
- Molecular regulations and therapeutic targets of Gaucher disease.Cytokine & growth factor reviews · 2018Review
- High mobility group box protein 1 downregulates acid β-glucosidase 1 in synovial fibroblasts from patients with rheumatoid arthritis.International journal of clinical and experimental pathology · 2018Article
- P38 delta MAPK promotes breast cancer progression and lung metastasis by enhancing cell proliferation and cell detachment.Oncogene · 2017Article
- Sphingolipids as a new factor in the pathomechanism of preeclampsia - Mass spectrometry analysis.PloS one · 2017Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Activation of protein kinase C (PKC) by the phorbol ester (phorbol 12-myristate 13-acetate) induces ceramide formation through the salvage pathway involving, in part, acid beta-glucosidase 1 (GBA1), which cleaves glucosylceramide to ceramide. Here, we examine the role of the GBA1-ceramide pathway, in regulating a pro-inflammatory pathway initiated by PKC and leading to activation of p38 and induction of interleukin 6 (IL-6). Inhibition of ceramide formation by fumonisin B1 or down-regulation of PKCdelta potentiated PMA-induced activation of p38 in human breast cancer MCF-7 cells. Similarly, knockdown of GBA1 by small interfering RNAs or pharmacological inhibition of GBA1 promoted further activation of p38 after PMA treatment, implicating the GBA1-ceramide pathway in the termination of p38 activation. Knockdown of GBA1 also evoked the hyperproduction of IL-6 in response to 4beta phorbol 12-myristate 13-acetate. On the other hand, increasing cellular ceramide with cell-permeable ceramide treatment resulted in attenuation of the IL-6 response. Importantly, silencing the delta isoform of the p38 family significantly attenuated the hyperproduction of IL-6. Reciprocally, p38delta overexpression induced IL-6 biosynthesis. Thus, the GBA1-ceramide pathway is suggested to play an important role in terminating p38delta activation responsible for IL-6 biosynthesis. Furthermore, the p38delta isoform was identified as a novel and predominant target of ceramide signaling as well as a regulator of IL-6 biosynthesis.
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Registered trials
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