Dissociation of apoptosis induction and CD36 upregulation by enzymatically modified low-density lipoprotein in monocytic cells.
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.
Jostarndt
Kristina
K
Institute for Prevention of Cardiovascular Diseases, Ludwig Maximilians University, Munich, Germany.
Gellert
Nina
N
Rubic
Tina
T
Weber
Christian
C
Kühn
Hartmut
H
Johansen
Berit
B
Hrboticky
Nina
N
Neuzil
Jiri
J
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
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