Why the study?
Does exposure to modified LDL stimulate the sphingomyelin-ceramide pathway in human macrophages?
Does exposure to modified LDL stimulate the sphingomyelin-ceramide pathway in human macrophages?
Modified LDL stimulates the sphingomyelin-ceramide pathway in human macrophages, suggesting its atherogenic effects are partly mediated by increased ceramide levels.
Supports ceramide pathway hypothesis in atherosclerosis models; leaves open translation to human macrophages in vivo.
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.
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Kinscherf et al. (1997) studied this question.
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