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The scavenger receptor class B, type I is a primary determinant of paraoxonase-1 association with high-density lipoproteins

Singh, Anurag Kumar
Riederer, Brigitte
Seidler, Ursula
Out, Ruud
Van Berkel, Theo J. C.
Published in Arteriosclerosis, Thrombosis, and Vascular Biology. 2010, vol. 30, no. 11, p. 2121-2127
Abstract OBJECTIVE: To examine the contribution of the scavenger receptor (SR) BI to the mechanism by which high-density lipoprotein (HDL) acquires paraoxonase-1 (PON1). METHODS AND 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.
Keywords AnimalsAntioxidants/metabolismAryldialkylphosphatase/blood/genetics/*metabolismCells, CulturedCricetinaeDown-RegulationGene ExpressionHumansLipoproteins, HDL/*metabolismScavenger Receptors, Class B/genetics/*metabolism
PMID: 20724701
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Research group Lipoprotéines sériques (598)
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JAMES, Richard William et al. The scavenger receptor class B, type I is a primary determinant of paraoxonase-1 association with high-density lipoproteins. In: Arteriosclerosis, Thrombosis, and Vascular Biology, 2010, vol. 30, n° 11, p. 2121-2127. doi: 10.1161/ATVBAHA.110.209122 https://archive-ouverte.unige.ch/unige:21025

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Deposited on : 2012-05-23

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