Modified low density lipoprotein delivers substrate for ceramide formation and stimulates the sphingomyelin-ceramide pathway in human macrophages |
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| Institution: | 1. Pharmazeutisch-Chemisches Institut, Universität Heidelberg, 69120 Heidelberg, Germany;2. Institut für Anatomie und Zellbiologie III, Universität Heidelberg, 69120 Heidelberg, Germany;3. Institut für Immunologie, Universität Heidelberg, 69120 Heidelberg, Germany;4. Deutsches Krebsforschungszentrum, 69120 Heidelberg, Germany;5. Institut für Biochemie und Lebensmittelchemie, Technische Universität, 8010 Graz, Austria;6. Klinikum der Friedrich-Schiller-Universität Jena, 07740 Jena, Germany |
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| Abstract: | Exposure of human blood monocytes derived macrophages to modified (oxidized or acetylated) LDL induced a ∼40% elevation (60 pmol/106 cells) of the endogenous level of the sphingolipid ceramide. A rise of both neutral and acidic SMase activity was found after treatment with oxidized LDL (250 and 80%), while addition of acLDL stimulated only the neutral enzyme (280%). Sphingo(phospho)lipids from LDL were transferred to the cell membrane and distributed into intracellular compartments as observed with acLDL containing BODIPY-FL-C5-SM. Quantitation of ceramide after the addition of 3H-N-acetyl]- or BODIPY-FL-C5-SM-labeled modified LDL (27 μg/ml) to the cell culture medium indicated that approximately 210 pmol CA/106 cells was generated from exogenous (ox/acLDL) SM. These results demonstrate a stimulation of the sphingomyelin-ceramide pathway by modified LDL utilizing primarily exogenous (LDL-derived) substrate and suggest that the effects of modified LDL are at least partially due to an increased level of the messenger ceramide.© 1997 Federation of European Biochemical Societies. |
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