UNIGE document Scientific Article
previous document  unige:21025  next document
add to browser collection
Title

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

Authors
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
Identifiers
PMID: 20724701
Full text
Article - document accessible for UNIGE members only Limited access to UNIGE
Structures
Research group Lipoprotéines sériques (598)
Citation
(ISO format)
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. https://archive-ouverte.unige.ch/unige:21025

234 hits

0 download

Update

Deposited on : 2012-05-23

Export document
Format :
Citation style :