The scavenger receptor class B, type I is a primary determinant of paraoxonase-1 association with high-density lipoproteins.
OBJECTIVE
To examine the contribution of the scavenger receptor (SR) BI to the mechanism by which high-density lipoprotein (HDL) acquires paraoxonase-1 (PON1).


RESULTS
Serum PON1 activity contributes to the antioxidant capacity of HDLs and is suggested to be an independent risk factor for atherosclerosis. The association of PON1 with HDL is a major determinant of its serum activity levels. PON1 secretion was studied in stably transfected Chinese hamster ovary and HepG2 models. Complementary analyses were performed in transgenic models. Modulation of SR-BI expression, by SR-BI small and interfering RNA knockdown and pharmacologically, correlated with significant changes (P<0.01) in PON1 secretion to HDLs and very-low-density lipoproteins. Block lipid transport-1 (BLT1), which increases the affinity of HDL for SR-BI without modulating its expression, was associated with significant increases in secretion. Downregulating postsynaptic density 95/disc-large/zona occludens kinase in HepG2 reduced cell SR-BI protein and lowered enzyme secretion. Serum PON1 activity was significantly reduced in postsynaptic density 95/disc-large/zona occludens kinase knockout mice.


CONCLUSIONS
The present study identifies SR-BI as a major determinant of the capacity of HDL to acquire PON1. It reinforces the concept of the receptor as a docking molecule, allowing communication between HDL and the cell, and extends the importance of SR-BI to HDL metabolism and function.
James
Richard W
RW
Clinical Diabetes Unit, Department of Internal Medicine, Geneva University Hospital, 4 rue Gabrielle-Perret-Gentil, 1211 Geneva 4, Switzerland. Richard.James@hcuge.ch
Brulhart-Meynet
Marie-Claude
MC
Singh
Anurag Kumar
AK
Riederer
Brigitte
B
Seidler
Ursula
U
Out
Ruud
R
Van Berkel
Theo J C
TJ
Deakin
Sara
S
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D043303:Aryldialkylphosphatase / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D006224:Cricetinae; D015536:Down-Regulation; D015870:Gene Expression; D006801:Humans; D008075:Lipoproteins, HDL / Q000378:metabolism*; D051122:Scavenger Receptors, Class B / Q000235:genetics / Q000378:metabolism*
D000975:Antioxidants; D008075:Lipoproteins, HDL; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B; D043303:Aryldialkylphosphatase