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Journal of Lipid Research, Vol. 44, 331-341, February 2003
Copyright © 2003 by Lipid Research, Inc.
* Department of Pharmacological Sciences, University Medical Center, State University of New York at Stony Brook, Stony Brook, NY 11794-8651
Division of Gastroenterology and Nutrition, Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104
1 To whom correspondence should be addressed. e-mail: connelly{at}pharm.sunysb.edu
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.
Abbreviations: ACEH, acid cholesteryl ester hydrolase; ACTH, adrenocorticotropic hormone; CE, cholesteryl ester; ECD, extracellular domain; FC, free cholesterol; [3H]CE, [3H]cholesteryl oleate; NCEH, neutral cholesteryl ester hydrolase; PMA, phorbol 12-myristate 13-acetate; RCT, reverse cholesterol transport; SR-BI, scavenger receptor class B type I; SU, selective uptake; UBP, diethylumbelliferyl phosphate
Supplementary key words scavenger receptor class B type I • reverse cholesterol transport • selective uptake • CD36 • cholesteryl oleyl ether • neutral cholesteryl ester hydrolase • adrenocorticotropic hormone • high density lipoprotein • low density lipoprotein
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