en
Scientific article
English

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

Published inArteriosclerosis, thrombosis, and vascular biology, vol. 30, no. 11, p. 2121-2127
Publication date2010
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
  • Animals
  • Antioxidants/metabolism
  • Aryldialkylphosphatase/blood/genetics/*metabolism
  • Cells, Cultured
  • Cricetinae
  • Down-Regulation
  • Gene Expression
  • Humans
  • Lipoproteins, HDL/*metabolism
  • Scavenger Receptors, Class B/genetics/*metabolism
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. doi: 10.1161/ATVBAHA.110.209122
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ISSN of the journal1079-5642
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