Modified low density lipoprotein delivers substrate for ceramide formation and stimulates the sphingomyelin-ceramide pathway in human macrophages

Autor: Volker Daniel, Jürgen Metz, Christoph Gehrke, Stefan Dr. Rußwurm, Olaf Nauen, Hans P. Deigner, Volker Hack, Albin Hermetter, Ralf Claus, Ralf Kinscherf
Rok vydání: 1997
Předmět:
Zdroj: FEBS letters. 405(1)
ISSN: 0014-5793
Popis: 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.
Databáze: OpenAIRE