ArticleThe Journal of biological chemistry2015
Expression of Ceramide Synthase 6 Transcriptionally Activates Acid Ceramidase in a c-Jun N-terminal Kinase (JNK)-dependent Manner.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 37 citations in OpenAlex.
- Article
- Lipid metabolic reprogramming in colorectal cancer: Insights to mechanisms and therapeutics.World journal of gastrointestinal oncology · 2025Review
- Advances in ORMDL Research in Malignant Tumors: A Review.OncoTargets and therapy · 2025Review
- How ceramides affect the development of colon cancer: from normal colon to carcinoma.Pflugers Archiv : European journal of physiology · 2024Review
- Therapeutic Potential for Sphingolipids in Inflammatory Bowel Disease and Colorectal Cancer.Cancers · 2024Review
- Integrated Transcriptomics and Metabolomics Reveal Changes in Cell Homeostasis and Energy Metabolism inInternational journal of molecular sciences · 2024Article
- The ceramide synthase (CERS/LASS) family: Functions involved in cancer progression.Cellular oncology (Dordrecht, Netherlands) · 2023Review
- Mass Spectrometry Detects Sphingolipid Metabolites for Discovery of New Strategy for Cancer Therapy from the Aspect of Programmed Cell Death.Metabolites · 2023Review
- S1PR1 induces metabolic reprogramming of ceramide in vascular endothelial cells, affecting hepatocellular carcinoma angiogenesis and progression.Cell death & disease · 2022Article
- Sphingolipid Metabolism and Signaling in Lung Cancer: A Potential Therapeutic Target.Journal of oncology · 2022Review
- Comprehensive analysis of LASS6 expression and prognostic value in ovarian cancer.Journal of ovarian research · 2021Article
- Skin Mast Cell-Driven Ceramides Drive Early Apoptosis in Pre-Symptomatic Eczema in Mice.International journal of molecular sciences · 2021Article
- Ceramide Synthase 6 Maximizes p53 Function to Prevent Progeny Formation from Polyploid Giant Cancer Cells.Cancers · 2021Article
- Elusive Roles of the Different Ceramidases in Human Health, Pathophysiology, and Tissue Regeneration.Cells · 2020Review
- Analysis of the uterine lumen in fertility-classified heifers: I. Glucose, prostaglandins, and lipids†.Biology of reproduction · 2020Article
- Genetic and pharmacological inhibition of acid ceramidase prevents asymmetric cell division by neosis.Journal of lipid research · 2019Article
- Expression of the SNAI2 transcriptional repressor is regulated by CCancer biology & therapy · 2019Article
- Molecular Targeting of Acid Ceramidase in Glioblastoma: A Review of Its Role, Potential Treatment, and Challenges.Pharmaceutics · 2018Review
- Decreased ceramide underlies mitochondrial dysfunction in Charcot-Marie-Tooth 2F.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2018Article
- Ceramide Synthase 6 Deficiency Enhances Inflammation in the DSS model of Colitis.Scientific reports · 2018Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
A family of six ceramide synthases with distinct but overlapping substrate specificities is responsible for generation of ceramides with acyl chains ranging from ∼14-26 carbons. Ceramide synthase 6 (CerS6) preferentially generates C14- and C16-ceramides, and we have previously shown that down-regulation of this enzyme decreases apoptotic susceptibility. In this study, we further evaluated how increased CerS6 expression impacts sphingolipid composition and metabolism. Overexpression of CerS6 in HT29 colon cancer cells resulted in increased apoptotic susceptibility and preferential generation of C16-ceramide, which occurred at the expense of very long chain, saturated ceramides. These changes were also reflected in sphingomyelin composition. HT-CerS6 cells had increased intracellular levels of sphingosine, which is generated by ceramidases upon hydrolysis of ceramide. qRT-PCR analysis revealed that only expression of acid ceramidase (ASAH1) was increased. The increase in acid ceramidase was confirmed by expression and activity analyses. Pharmacological inhibition of JNK (SP600125) or curcumin reduced transcriptional up-regulation of acid ceramidase. Using an acid ceramidase promoter driven luciferase reporter plasmid, we demonstrated that CerS1 has no effect on transcriptional activation of acid ceramidase and that CerS2 slightly but significantly decreased the luciferase signal. Similar to CerS6, overexpression of CerS3-5 resulted in an ∼2-fold increase in luciferase reporter gene activity. Exogenous ceramide failed to induce reporter activity, while a CerS inhibitor and a catalytically inactive mutant of CerS6 failed to reduce it. Taken together, these results suggest that increased expression of CerS6 can mediate transcriptional activation of acid ceramidase in a JNK-dependent manner that is independent of CerS6 activity.
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