Hypochlorite-oxidized low-density lipoprotein upregulates CD36 and PPARgamma mRNA expression and modulates SR-BI gene expression in murine macrophages.
The uptake of oxidized low-density lipoprotein (oxLDL) by scavenger receptors of macrophages with resulting foam cell formation is considered a critical event in atherogenesis. Since hypochlorite-oxidized LDL (HOCl-LDL) has been shown to be recognized by macrophages and evidence was provided that HOCl-LDL is internalized via class B scavenger receptors CD36 and SR-BI, the regulatory relationships between CD36, SR-BI, and the nuclear transcription factor PPARgamma in murine macrophages (RAW 264.7) on exposure to HOCl-LDL were examined. Using the highly sensitive real-time RT-PCR we could demonstrate that HOCl-LDL upregulated CD36 and PPARgamma levels dose- and time dependently while modulating SR-BI message levels differently in dependence on HOCl-LDL concentration and incubation time. On exposure of macrophages to HOCl-LDL but not native LDL in varying concentrations, a significant positive correlation between CD36 and PPARgamma (rho = 0.603, p = 0.001) was observed indicating the presence of a positive feedback mechanism by which HOCl-LDL could promote its own uptake. The transcriptional expression of SR-BI in macrophages was not significantly related to PPARgamma mRNA levels after treatment with HOCl-LDL suggesting a differential regulation of the two members of the scavenger receptor class B family in response to HOCl-LDL.
Westendorf
Thomas
T
Department of Internal Medicine III, Pathological Biochemistry, Carl Gustav Carus Medical School, University of Technology, Dresden, Germany.
Graessler
Juergen
J
Kopprasch
Steffi
S
D000818:Animals; D001483:Base Sequence; D018955:CD36 Antigens / Q000235:genetics*; D002460:Cell Line; D018932:Chemokine CCL2 / Q000096:biosynthesis; D004247:DNA / Q000235:genetics; D006997:Hypochlorous Acid / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000378:metabolism / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D047495:PPAR gamma / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D015854:Up-Regulation / Q000187:drug effects
D018955:CD36 Antigens; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D008077:Lipoproteins, LDL; D047495:PPAR gamma; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C099252:oxidized low density lipoprotein; D006997:Hypochlorous Acid; D004247:DNA