SR-BI-directed HDL-cholesteryl ester hydrolysis.
We have examined the metabolic fate of HDL cholesteryl ester (CE) delivered to cells expressing scavenger receptor class B type I (SR-BI). Comparison of SR-BI with a related class B scavenger receptor, CD36, showed a greater uptake and a more rapid and extensive hydrolysis of HDL-CE when delivered by SR-BI. In addition, hydrolysis of HDL-CE delivered by both receptors was via a neutral CE hydrolase. These data indicate that SR-BI, but not CD36, can efficiently direct HDL-CE to a neutral CE hydrolytic pathway. In contrast, LDL-CE was delivered and hydrolyzed equally well by SR-BI and CD36. Hydrolysis of LDL-CE delivered by SR-BI was via a neutral CE hydrolase but that delivered by CD36 occurred via an acidic CE hydrolase, indicating that SR-BI and CD36 deliver LDL-CE to different metabolic pathways. Comparison of inhibitor sensitivities in Y1-BS1 adrenal, Fu5AH hepatoma, and transfected cells suggests that hydrolysis of HDL-CE delivered by SR-BI occurs via cell type-specific neutral CE hydrolases. Furthermore, HDL-CE hydrolytic activity was recovered in a membrane fraction of Y1-BS1 cells. These findings suggest that SR-BI efficiently delivers HDL-CE to a metabolically active membrane compartment where CE is hydrolyzed by a neutral CE hydrolase.
Connelly
Margery A
MA
Department of Pharmacological Sciences, University Medical Center, State University of New York at Stony Brook, Stony Brook, NY 11794-8651, USA. connelly@pharm.sunysb.edu
Kellner-Weibel
Ginny
G
Rothblat
George H
GH
Williams
David L
DL
D000818:Animals; D018955:CD36 Antigens / Q000378:metabolism*; D002460:Cell Line; D002788:Cholesterol Esters / Q000378:metabolism*; D008078:Cholesterol, LDL / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008565:Membrane Proteins; D051381:Rats; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein / Q000378:metabolism*; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B; D013347:Subcellular Fractions / Q000378:metabolism
D018955:CD36 Antigens; D002788:Cholesterol Esters; D008078:Cholesterol, LDL; C059714:HDL cholesteryl ester; D008075:Lipoproteins, HDL; D008565:Membrane Proteins; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C495124:SCARB1 protein, human; C454739:Scarb1 protein, mouse; C495125:Scarb1 protein, rat; D051122:Scavenger Receptors, Class B