Inhibition of phosphatidylcholine and phosphatidylethanolamine biosynthesis in rat-2 fibroblasts by cell-permeable ceramides.

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  • Additional Information
    • Source:
      Publisher: Blackwell Science Ltd. on behalf of the Federation of European Biochemical Societies Country of Publication: England NLM ID: 0107600 Publication Model: Print Cited Medium: Print ISSN: 0014-2956 (Print) Linking ISSN: 00142956 NLM ISO Abbreviation: Eur J Biochem Subsets: MEDLINE
    • Publication Information:
      Publication: -2004: Oxford, UK : Blackwell Science Ltd. on behalf of the Federation of European Biochemical Societies
      Original Publication: Berlin, New York, Springer.
    • Subject Terms:
      Ceramides/*pharmacology ; Phosphatidylcholines/*antagonists & inhibitors ; Phosphatidylethanolamines/*antagonists & inhibitors; Animals ; Apoptosis/drug effects ; Cell Line ; Cell Membrane Permeability ; Ceramides/metabolism ; Choline/metabolism ; Diglycerides/biosynthesis ; Diglycerides/metabolism ; Dose-Response Relationship, Drug ; Ethanolamine/metabolism ; Fibroblasts/cytology ; Fibroblasts/drug effects ; Palmitic Acid/metabolism ; Phosphatidylcholines/biosynthesis ; Phosphatidylethanolamines/biosynthesis ; Rats
    • Abstract:
      Phospholipids and sphingolipids are important precursors of lipid-derived second messengers such as diacylglycerol and ceramide, which participate in several signal transduction pathways and in that way mediate the effects of various agonists. The cross-talk between glycerophospholipid and sphingolipid metabolism was investigated by examining the effects of cell-permeable ceramides on phosphatidylcholine (PtdCho) and phosphatidylethanolamine (PtdEtn) synthesis in Rat-2 fibroblasts. Addition of short-chain C6-ceramide to the cells resulted in a dose- and time-dependent inhibition of the CDP-pathways for PtdCho and PtdEtn synthesis. Treatment of cells for 4 h with 50 microM C6-ceramide caused an 83% and a 56% decrease in incorporation of radiolabelled choline and ethanolamine into PtdCho and PtdEtn, respectively. Exposure of the cells for longer time-periods (>/= 16 h) to 50 microM C6-ceramide resulted in apoptosis. The structural analogue dihydro-C6-ceramide did not affect PtdCho and PtdEtn synthesis. In pulse-chase experiments, radioactive choline and ethanolamine accumulated in CDP-choline and CDP-ethanolamine under the influence of C6-ceramide, suggesting that synthesis of both PtdCho and PtdEtn were inhibited at the final step in the CDP-pathways. Indeed, cholinephosphotransferase and ethanolaminephosphotransferase activities in membrane fractions from C6-ceramide-treated cells were reduced by 64% and 43%, respectively, when compared with control cells. No changes in diacylglycerol mass levels or synthesis of diacylglycerol from radiolabelled palmitate were observed. It was concluded that C6-ceramide affected glycerophospholipid synthesis predominantly by inhibition of the step in the CDP-pathways catalysed by cholinephosphotransferase and ethanolaminephosphotransferase.
    • Accession Number:
      0 (Ceramides)
      0 (Diglycerides)
      0 (Phosphatidylcholines)
      0 (Phosphatidylethanolamines)
      2V16EO95H1 (Palmitic Acid)
      5KV86114PT (Ethanolamine)
      N91BDP6H0X (Choline)
    • Publication Date:
      Date Created: 19990814 Date Completed: 19990921 Latest Revision: 20190620
    • Publication Date:
      20240829
    • Accession Number:
      10.1046/j.1432-1327.1999.00589.x
    • Accession Number:
      10447683