title: Dissociation of apoptosis induction and CD36 upregulation by enzymatically modified low-density lipoprotein in monocytic cells.
abstract: Modified low-density lipoprotein (LDL) has been implicated as an initiating or amplifying factor in atherogenesis. Some of its biological activities, such as apoptosis induction and upregulation of the scavenger receptor CD36, appear to share common signaling pathways in cells of the cardiovascular system. Exposure of low-differentiated monocytic cells to LDL modified with 15-lipoxygenase and secretory phospholipase A(2) induced apoptosis and upregulated CD36. Cell treatment with constituents of modified LDL, such as 13-hydroxyoctadecadienoic acid (13-HODE), 25-hydroxycholesterol, and lysophosphatidyl choline, and with an unrelated apoptogen (TNF-related apoptosis-inducing ligand) induced apoptosis. In contrast, only 13-HODE caused upregulation of CD36 expression. Cotreatment with the pan-caspase inhibitor z.VAD-fmk resulted in suppression of apoptosis, but was without any effect on CD36 expression. These data indicate that in monocytic cells enzymatically modified LDL is capable of inducing both apoptosis and upregulation of CD36 expression. However, in our cellular model, the two induction processes appear to be causally unrelated.
authors.affiliation: Institute for Prevention of Cardiovascular Diseases, Ludwig Maximilians University, Munich, Germany.
authors.forename: Kristina
authors.initials: K
authors.lastname: Jostarndt
authors.forename: Nina
authors.initials: N
authors.lastname: Gellert
authors.forename: Tina
authors.initials: T
authors.lastname: Rubic
authors.forename: Christian
authors.initials: C
authors.lastname: Weber
authors.forename: Hartmut
authors.initials: H
authors.lastname: Kühn
authors.forename: Berit
authors.initials: B
authors.lastname: Johansen
authors.forename: Nina
authors.initials: N
authors.lastname: Hrboticky
authors.forename: Jiri
authors.initials: J
authors.lastname: Neuzil
mesh_terms: D017209:Apoptosis; D001093:Arachidonate 15-Lipoxygenase / Q000378:metabolism; D018955:CD36 Antigens / Q000096:biosynthesis*; D002460:Cell Line; D006801:Humans; D008041:Linoleic Acids / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000378:metabolism* / Q000494:pharmacology*; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010741:Phospholipases A / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D015533:Transcriptional Activation; D015854:Up-Regulation
chemical_list: D018955:CD36 Antigens; D008041:Linoleic Acids; D008077:Lipoproteins, LDL; D012333:RNA, Messenger; C024348:13-hydroxy-9,11-octadecadienoic acid; D001093:Arachidonate 15-Lipoxygenase; D010741:Phospholipases A