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cis-4-Methylsphingosine Phosphate Induces Apoptosis in Neuroblastoma Cells by Opposite Effects on p38 and ERK Mitogen-Activated Protein Kinases

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Published/Copyright: June 1, 2005
Biological Chemistry
From the journal Volume 383 Issue 12

Abstract

Intracellular phosphorylation of cis-4-methylsphingosine was previously shown to result in a metabolically stable compound that accumulates in Swiss 3T3 fibroblasts and mimics the mitogenic effect induced by the shortlived sphingosine metabolite, sphingosine 1-phosphate. In the present study incubation of neuroblastoma B104 cells with cis-4-methylsphingosine (10 M) also resulted in an intracellular accumulation of its phosphorylated derivative that was, however, associated with the concentrationdependent induction of apoptosis, not observed after treatment with 10 M of sphingosine-1-phosphate or sphingosine, respectively. In B104 cells, cis-4-methylsphingosine stimulated p38 mitogenactivated protein kinase (p38 MAPK) and simultaneously inhibited extracellular signalregulated kinase (ERK), whereas sphingosine and sphingosine 1-phosphate only stimulated p38 MAPK without suppression of ERK. Inhibition of cis-4-methylsphingosine phosphorylation reduced both, apoptosis and concurrent regulation of mitogenactivated protein kinases (MAPKs), suggesting that the unusual accumulation of the phosphorylated sphingoid base was responsible for the biological effects. Furthermore, inhibition of p38 MAPK prevented cis-4-methylsphingosineinduced apoptosis, while suppression of the ERK pathway in the presence of sphingosine or sphingosine-1-phosphate resulted in apoptosis, indicating that the simultaneous opposite regulation of the two MAPKs was required for the induction of apoptosis.

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Published Online: 2005-06-01
Published in Print: 2002-12-09

Copyright © 2002 by Walter de Gruyter GmbH & Co. KG

Articles in the same Issue

  1. Processing and Activation of Lysosomal Proteinases
  2. Evidence That E-Box Promoter Elements and MyoD Transcription Factors Play a Role in the Induction of Cathepsin B Gene Expression during Human Myoblast Differentiation
  3. Transcription Factor Egr-1 Activates Collagen Expression in Immortalized Fibroblasts or Fibrosarcoma Cells
  4. The Receptor-Bound N-Terminal Ectodomain of the Amyloid Precursor Protein Is Associated with Membrane Rafts
  5. Evaluation of Similarities in the cis/trans Isomerase Function of Trigger Factor and DnaK
  6. The Chloroplast Import Receptor Toc34 Functions as Preprotein-Regulated GTPase
  7. cis-4-Methylsphingosine Phosphate Induces Apoptosis in Neuroblastoma Cells by Opposite Effects on p38 and ERK Mitogen-Activated Protein Kinases
  8. Evidence for the Involvement of the Unique C-Tail of S100A9 in the Binding of Arachidonic Acid to the Heterocomplex S100A8/A9
  9. The Primary Structure of Three Hemoglobin Chains from the Indigo Snake (Drymarchon corais erebennus, Serpentes): First Evidence for αD Chains and Two β Chain Types in Snakes
  10. Expression of the Tissue Kallikrein-Kinin Cascade in Granulosa Cells of the Ovary
  11. Chondroitin Sulfate Proteoglycan Is a Potent Enhancer in the Processing of Procathepsin L
  12. Tyrosinase-Mediated Oxidation of Acetaminophen to 4-Acetamido-o- Benzoquinone
  13. Properties of Baculovirus Particles Displaying GFP Analyzed by Fluorescence Correlation Spectroscopy
  14. The Promoter Context Determines Mutual Repression or Synergism between NF-κB and the Glucocorticoid Receptor
  15. Expression of Hepatocyte Growth Factor Activator Inhibitor Type 2 (HAI-2) in Human Testis: Identification of a Distinct Transcription Start Site for the HAI-2 Gene in Testis
  16. Identification and Characterization of an IgG Binding Protein in the Secretion of the Rat Coagulating Gland
  17. Characterization of Different Reactive Lysines in Bovine Heart Mitochondrial Porin
  18. Determination of the mRNA Sequence of Cathepsin Y, a Cysteine Endopeptidase from Rat Spleen, and Confirmation of Its Ubiquitous
  19. Acknowledgement
  20. Content Index
  21. Author Index
  22. Subject Index
https://doi.org/10.1515/BC.2002.212

Articles in the same Issue

  1. Processing and Activation of Lysosomal Proteinases
  2. Evidence That E-Box Promoter Elements and MyoD Transcription Factors Play a Role in the Induction of Cathepsin B Gene Expression during Human Myoblast Differentiation
  3. Transcription Factor Egr-1 Activates Collagen Expression in Immortalized Fibroblasts or Fibrosarcoma Cells
  4. The Receptor-Bound N-Terminal Ectodomain of the Amyloid Precursor Protein Is Associated with Membrane Rafts
  5. Evaluation of Similarities in the cis/trans Isomerase Function of Trigger Factor and DnaK
  6. The Chloroplast Import Receptor Toc34 Functions as Preprotein-Regulated GTPase
  7. cis-4-Methylsphingosine Phosphate Induces Apoptosis in Neuroblastoma Cells by Opposite Effects on p38 and ERK Mitogen-Activated Protein Kinases
  8. Evidence for the Involvement of the Unique C-Tail of S100A9 in the Binding of Arachidonic Acid to the Heterocomplex S100A8/A9
  9. The Primary Structure of Three Hemoglobin Chains from the Indigo Snake (Drymarchon corais erebennus, Serpentes): First Evidence for αD Chains and Two β Chain Types in Snakes
  10. Expression of the Tissue Kallikrein-Kinin Cascade in Granulosa Cells of the Ovary
  11. Chondroitin Sulfate Proteoglycan Is a Potent Enhancer in the Processing of Procathepsin L
  12. Tyrosinase-Mediated Oxidation of Acetaminophen to 4-Acetamido-o- Benzoquinone
  13. Properties of Baculovirus Particles Displaying GFP Analyzed by Fluorescence Correlation Spectroscopy
  14. The Promoter Context Determines Mutual Repression or Synergism between NF-κB and the Glucocorticoid Receptor
  15. Expression of Hepatocyte Growth Factor Activator Inhibitor Type 2 (HAI-2) in Human Testis: Identification of a Distinct Transcription Start Site for the HAI-2 Gene in Testis
  16. Identification and Characterization of an IgG Binding Protein in the Secretion of the Rat Coagulating Gland
  17. Characterization of Different Reactive Lysines in Bovine Heart Mitochondrial Porin
  18. Determination of the mRNA Sequence of Cathepsin Y, a Cysteine Endopeptidase from Rat Spleen, and Confirmation of Its Ubiquitous
  19. Acknowledgement
  20. Content Index
  21. Author Index
  22. Subject Index
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