Scavenger receptor class B type I is solely responsible for the selective uptake of cholesteryl esters from HDL by the liver and the adrenals in mice.
Scavenger receptor class B type I (SR-BI) has been identified as a functional HDL binding protein that can mediate the selective uptake of cholesteryl ester (CE) from HDL. To quantify the in vivo role of SR-BI in the process of selective uptake, HDL was labeled with cholesteryl ether ([(3)H] CEt-HDL) and (125)I-tyramine cellobiose ([(125)I]TC-HDL) and injected into SR-BI knockout (KO) and wild-type (WT) mice. In SR-BI KO mice, the clearance of HDL-CE from the blood circulation was greatly diminished (0.043 +/- 0.004 pools/h for SR-BI KO mice vs. 0.106 +/- 0.004 pools/h for WT mice), while liver and adrenal uptake were greatly reduced. Utilization of double-labeled HDL ([(3)H]CEt and [(125)I]TC) indicated the total absence in vivo of the selective decay and liver uptake of CE from HDL in SR-BI KO mice. Parenchymal cells isolated from SR-BI KO mice showed similar association values for [(3)H]CEt and [(125)I]TC in contrast to WT cells, indicating that in parenchymal liver cells SR-BI is the only molecule exerting selective CE uptake from HDL. Thus, in vivo and in vitro, SR-BI is the sole molecule mediating the selective uptake of CE from HDL by the liver and the adrenals, making it the unique target to modulate reverse cholesterol transport.
Leiden/Amsterdam Center for Drug Research, Division of Biopharmaceutics, Gorlaeus Laboratories, Leiden University, 2300 RA Leiden, The Netherlands.
Ruud
R
Out
Menno
M
Hoekstra
John A A
JA
Spijkers
Johan K
JK
Kruijt
Miranda
M
van Eck
Ingrid S T
IS
Bos
Jaap
J
Twisk
Theo J C
TJ
Van Berkel
D000311:Adrenal Glands / Q000378:metabolism*; D000818:Animals; D018955:CD36 Antigens; D002784:Cholesterol / Q000378:metabolism; D002788:Cholesterol Esters / Q000378:metabolism / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D005260:Female; D022781:Hepatocytes / Q000378:metabolism; D006579:Heterozygote; D006801:Humans; D008024:Ligands; D008074:Lipoproteins / Q000378:metabolism; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010743:Phospholipids / Q000737:chemistry; D011971:Receptors, Immunologic / Q000502:physiology*; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B; D013997:Time Factors
D018955:CD36 Antigens; D002788:Cholesterol Esters; D008024:Ligands; D008074:Lipoproteins; D008075:Lipoproteins, HDL; D010743:Phospholipids; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B; D002784:Cholesterol