Oxidized low density lipoprotein decreases macrophage expression of scavenger receptor B-I.
Scavenger receptor class B type I (SR-BI) has recently been identified as a high density lipoprotein (HDL) receptor that mediates bidirectional flux of cholesterol across the plasma membrane. We have previously demonstrated that oxidized low density lipoprotein (OxLDL) will increase expression of another class B scavenger receptor, CD36 (Han, J., Hajjar, D. P., Febbraio, M., and Nicholson, A. C. (1997) J. Biol. Chem. 272, 21654-21659). In studies reported herein, we evaluated the effects of OxLDL on expression of SR-BI in macrophages to determine how exposure to this modified lipoprotein could alter SR-BI expression and cellular lipid flux. OxLDL decreased SR-BI expression in a dose- and time-dependent manner. Incubation with OxLDL had no effect on the membrane distribution of SB-BI, and it decreased expression of both cytosolic and membrane protein. Consistent with its effect on SR-BI protein expression, OxLDL decreased SR-BI mRNA in a dose-dependent manner. The ability of OxLDL to decrease SR-BI expression was dependent on the degree of LDL oxidation. OxLDL decreased both [(14)C]cholesteryl oleate/HDL uptake and efflux of [(14)C]cholesterol to HDL in a time-dependent manner. Incubation of macrophages with 7-ketocholesterol, but not free cholesterol, also inhibited expression of SR-BI. Finally, we demonstrate that the effect of OxLDL on SR-BI is dependent on the differentiation state of the monocyte/macrophage. These results imply that in addition to its effect in inducing foam cell formation in macrophages through increased uptake of oxidized lipids, OxLDL may also enhance foam cell formation by altering SR-BI-mediated lipid flux across the cell membrane.
Center of Vascular Biology, Weill Medical College of Cornell University, New York, New York 10021, USA.
J
J
Han
A C
AC
Nicholson
X
X
Zhou
J
J
Feng
A M
AM
Gotto
D P
DP
Hajjar
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D018955:CD36 Antigens / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism / Q000494:pharmacology; D002788:Cholesterol Esters / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007653:Ketocholesterols / Q000494:pharmacology; D007700:Kinetics; D008075:Lipoproteins, HDL / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000502:physiology*; D008565:Membrane Proteins; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein / Q000235:genetics / Q000378:metabolism; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B; D014158:Transcription, Genetic / Q000187:drug effects*
D018955:CD36 Antigens; D002788:Cholesterol Esters; D007653:Ketocholesterols; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D008565:Membrane Proteins; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C495124:SCARB1 protein, human; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; C099252:oxidized low density lipoprotein; C014409:cholesteryl oleate; D002784:Cholesterol; C003001:7-ketocholesterol