title: Modified low density lipoprotein delivers substrate for ceramide formation and stimulates the sphingomyelin-ceramide pathway in human macrophages.
abstract: Exposure of human blood monocytes derived macrophages to modified (oxidized or acetylated) LDL induced a approximately 40% elevation (60 pmol/10(6) 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 microg/ml) to the cell culture medium indicated that approximately 210 pmol CA/10(6) 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.
authors.affiliation: Pharmazeutisch-Chemisches Institut, Universität Heidelberg, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Kinscherf
authors.forename: R
authors.initials: R
authors.lastname: Claus
authors.forename: H P
authors.initials: HP
authors.lastname: Deigner
authors.forename: O
authors.initials: O
authors.lastname: Nauen
authors.forename: C
authors.initials: C
authors.lastname: Gehrke
authors.forename: A
authors.initials: A
authors.lastname: Hermetter
authors.forename: S
authors.initials: S
authors.lastname: Russwurm
authors.forename: V
authors.initials: V
authors.lastname: Daniel
authors.forename: V
authors.initials: V
authors.lastname: Hack
authors.forename: J
authors.initials: J
authors.lastname: Metz
mesh_terms: D001896:Boron Compounds / Q000737:chemistry; D002478:Cells, Cultured; D002518:Ceramides / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology; D005456:Fluorescent Dyes / Q000737:chemistry; D006801:Humans; D008074:Lipoproteins / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D008297:Male; D010740:Phospholipases / Q000378:metabolism; D013109:Sphingomyelins / Q000378:metabolism*; D014316:Tritium
chemical_list: C095489:4,4-difluoro-4-bora-3a,4a-diaza-s-indacene; D001896:Boron Compounds; D002518:Ceramides; D005456:Fluorescent Dyes; D008074:Lipoproteins; D008077:Lipoproteins, LDL; D013109:Sphingomyelins; D014316:Tritium; D010740:Phospholipases