Scavenger receptor class B type I affects cholesterol homeostasis by magnifying cholesterol flux between cells and HDL.
Results from several laboratories clearly indicate that expression of scavenger receptor class B type I (SR-BI) enhances the bidirectional flux of cholesterol between cells and lipoproteins. Because the activity of HMG-CoA reductase, the key enzyme in cholesterol biosynthesis, is regulated by cell cholesterol content, we designed experiments to investigate the effect of SR-BI expression on the activity of this enzyme and on net cellular cholesterol mass. In addition, we compared the function of SR-BI with its human homolog, CD36 and LIMPII analogous 1. Our experiments demonstrate that both receptors enhance the flux of unesterified or free cholesterol bidirectionally, down a concentration gradient. Receptor-mediated cholesterol flux can effectively modulate multiple aspects of cellular cholesterol metabolism, including the pool that regulates the activity of HMG-CoA reductase. We also found that constitutive expression of SR-BI alters the steady state level of cellular cholesterol and phospholipid when SR-BI-expressing cells are maintained in medium containing serum lipoproteins. All of these effects are proportional to the level of receptor on the cell surface. These data indicate that the level of SR-BI expression determines both the rate of free cholesterol flux and the steady state level of cellular cholesterol.
de La Llera-Moya
M
M
Division of Gastroenterology and Nutrition, Department of Pediatrics, Abramson Research Center, Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-4318, USA. moya@email.chop.edu
Connelly
M A
MA
Drazul
D
D
Klein
S M
SM
Favari
E
E
Yancey
P G
PG
Williams
D L
DL
Rothblat
G H
GH
D000818:Animals; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism*; D019556:COS Cells; D002784:Cholesterol / Q000378:metabolism*; D002789:Cholesterol Oxidase / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D025782:Hydroxymethylglutaryl-CoA-Reductases, NADP-dependent / Q000378:metabolism; D008075:Lipoproteins, HDL / Q000378:metabolism*; D053440:Lipoproteins, HDL3; D008565:Membrane Proteins; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein / Q000378:metabolism; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B; D014162:Transfection
D018955:CD36 Antigens; D008075:Lipoproteins, HDL; D053440:Lipoproteins, HDL3; D008565:Membrane Proteins; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C495124:SCARB1 protein, human; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D002784:Cholesterol; D025782:Hydroxymethylglutaryl-CoA-Reductases, NADP-dependent; D002789:Cholesterol Oxidase