ArticleThe Biochemical journal1999
Activation of caspase-3-like proteases in apoptosis induced by sphingosine and other long-chain bases in Hep3B hepatoma cells.
Article in The Biochemical journal, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 82 citations in OpenAlex.
- Machine learning-based multi-omic analysis identifies CEP55, DLGAP5, and EZH2 as regulated cell death biomarkers linked to immunotherapy resistance in hepatocellular carcinoma.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Computational integration of in vivo single cell and in vitro bulk transcriptomics across 236 human and mouse datasets differentiates physiological versus non-physiological hepatic cell lines for hepatotoxicity screening.Toxicological sciences : an official journal of the Society of Toxicology · 2026Article
- Pathogens That Rewrite the Rules: Ascoviruses, Elegant Manipulators of Cell Death Pathways and Architects of the Extracellular Viral Paradigm.Pathogens (Basel, Switzerland) · 2025Review
- Role of sphingolipid metabolites in the homeostasis of steroid hormones and the maintenance of testicular functions.Frontiers in endocrinology · 2023Review
- Manifold Roles of Ceramide Metabolism in Non-Alcoholic Fatty Liver Disease and Liver Cancer.Advances in experimental medicine and biology · 2022Article
- Loss of genomic integrity induced by lysosphingolipid imbalance drives ageing in the heart.EMBO reports · 2019Article
- Deletion of sphingosine kinase 1 inhibits liver tumorigenesis in diethylnitrosamine-treated mice.Oncotarget · 2018Article
- "Dicing and Splicing" Sphingosine Kinase and Relevance to Cancer.International journal of molecular sciences · 2017Review
- Sphingolipids in mitochondria.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2017Review
- Caspase-3 mediated release of SAC domain containing fragment from Par-4 is necessary for the sphingosine-induced apoptosis in Jurkat cells.Journal of molecular signaling · 2013Article
- Targeting sphingosine-1-phosphate receptors in cancer.Anti-cancer agents in medicinal chemistry · 2011Review
- Article
- Regulation of phosphatidic Acid metabolism by sphingolipids in the central nervous system.Journal of lipids · 2011Article
- Review
- Deregulation of sphingolipid metabolism in Alzheimer's disease.Neurobiology of aging · 2010Article
- Sphingolipidomics: methods for the comprehensive analysis of sphingolipids.Journal of chromatography. B, Analytical technologies in the biomedical and life sciences · 2009Review
- Sphingosine-1-phosphate receptors: biology and therapeutic potential in kidney disease.Kidney international · 2008Review
- Sphingolipid therapy in myocardial ischemia-reperfusion injury.Biochimica et biophysica acta · 2008Review
- Multiple roles for sphingolipids in steroid hormone biosynthesis.Sub-cellular biochemistry · 2008Review
- Attenuated Leishmanial sphingolipid induces apoptosis in A375 human melanoma cell via both caspase-dependent and -independent pathways.Molecular and cellular biochemistry · 2007Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sphingosine and other long-chain bases (including sphinganine, dimethylsphingosine and stearylamine), but not octylamine (a short-chain analogue of sphinganine), induced apoptosis in Hep3B hepatoma cells. Because both D- and L-erythrosphingosine and stearylamine exert potent apoptotic effects on Hep3B cells, it is possible that these long-chain bases may activate apoptosis by inhibiting protein kinase C (PKC) activity. However, pretreatment with the PKC activator PMA could not rescue cells from apoptosis triggered by long-chain bases. Therefore the involvement of PKC in this apoptotic process requires further characterization. We also investigated whether these long-chain bases might be metabolized into ceramide in order to elicit their apoptotic action. We found that long-chain bases acted independently of ceramide in the induction of apoptosis, since addition of fumonisin B1, a fungal agent which effectively inhibits ceramide synthesis from sphingosine, did not protect against apoptosis. Additionally, we found that sphingosine-induced apoptosis was accompanied by activation of caspases. The functional role of caspases in this apoptotic process was examined by using specific caspase inhibitors. The general caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp fluoromethyl ketone, which exhibits a broad specificity for caspase-family proteases, effectively blocked sphingosine-induced apoptosis. Furthermore, our results indicate that caspase-3-like proteases, but not caspase-1, are activated during apoptosis triggered by sphingosine. Enhancement of caspase-3-like activity and cleavage of poly(ADP-ribose) polymerase, an in vivo substrate for caspase-3, was clearly demonstrated in sphingosine-treated Hep3B cells. Considered together, these results suggest that caspase-3-like proteases participate in apoptotic cell death induced by sphingosine.
Indexed as
Identifiers
9931312PMC1220038W1994648164What OpenQuestion holds
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.