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Class B scavenger receptors: Metabo...

Sun, Bing.

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Class B scavenger receptors: Metabolism of high density lipoprotein and oxidized low density lipoprotein.

Record Type:	Language materials, printed : Monograph/item
Title/Author:	Class B scavenger receptors: Metabolism of high density lipoprotein and oxidized low density lipoprotein./
Author:	Sun, Bing.
Description:	139 p.
Notes:	Advisers: Nancy R. Webb; Deneys R. Van Der Westhuyzen.
Contained By:	Dissertation Abstracts International68-04B.
Subject:	Health Sciences, Nutrition. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3259193

Class B scavenger receptors: Metabolism of high density lipoprotein and oxidized low density lipoprotein.
Sun, Bing.

Class B scavenger receptors: Metabolism of high density lipoprotein and oxidized low density lipoprotein. - 139 p.

Advisers: Nancy R. Webb; Deneys R. Van Der Westhuyzen.

Thesis (Ph.D.)--University of Kentucky, 2006.

Keywords. Class B Scavenger Receptors type I (SR-BI), CD36, Lipoprotein Metabolism, Selective CE uptake, Retroendocytosis.Subjects--Topical Terms:

1017801
Health Sciences, Nutrition.

Class B scavenger receptors: Metabolism of high density lipoprotein and oxidized low density lipoprotein.
LDR:05146nam 2200313 a 45 001 941523
005 20110519
008 110519s2006 eng d
035 $a (UMI)AAI3259193
035 $a AAI3259193
040 $a UMI $c UMI
100 1 $a Sun, Bing. $3 1265614
245 1 0 $a Class B scavenger receptors: Metabolism of high density lipoprotein and oxidized low density lipoprotein.
300 $a 139 p.
500 $a Advisers: Nancy R. Webb; Deneys R. Van Der Westhuyzen.
500 $a Source: Dissertation Abstracts International, Volume: 68-04, Section: B, page: 2265.
502 $a Thesis (Ph.D.)--University of Kentucky, 2006.
520 $a Keywords. Class B Scavenger Receptors type I (SR-BI), CD36, Lipoprotein Metabolism, Selective CE uptake, Retroendocytosis.
520 $a HDL and modified forms of LDL, including oxLDL, play pivotal roles in lipid accumulation in the vessel wall. One of the mechanisms by which HDL is believed to protect against atherosclerotic lipid deposition is through the ability to remove excess cholesterol from peripheral tissues including macrophages and deliver it to the liver. OxLDL contributes to lipid accumulation in macrophages that leads to foam cell formation. Therefore, it is important to understand the mechanisms by which cells metabolize HDL and oxLDL. It has been clearly established that class B scavenger receptors are important in the metabolism of HDL and oxLDL. Scavenger receptor class B, type I (SR-BI) is considered to be the principal receptor that mediates the selective transfer of cholesterol ester (CE) from HDL to the liver, and also mediates cellular free cholesterol (FC) efflux to HDL. CD36 is another member of class B scavenger receptor family that is closely related to SR-BI. It mediates the uptake and degradation of oxLDL by macrophages.
520 $a The mechanism of selective CE uptake by SR-BI remains controversial. Previous studies have suggested that in certain cell types, HDL retroendocytosis may play a role in SR-BI-dependent selective lipid uptake. To investigate this possibility, we developed new methods to quantitatively measure HDL uptake and re-secretion in fibroblast (COS-7) and hepatocyte (HepG2) cells expressing exogenous SR-BI. The results show that for both COS-7 and HepG2 cells, the rate of HDL secretion from the retroendocytic pool is too slow to account for the majority of selective CE uptake. However, the rate of release of surface bound HDL is fast enough to account for selective CE uptake. These indicate that SR-BI-dependent selective lipid uptake in hepatocytes and fibroblasts occurs mainly at the cell surface.
520 $a It is clear that SR-BI promotes selective lipid transfer through a mechanism that involves more than mere docking of the HDL particle to the cell surface. This is suggested by the observation that CD36 does not mediate efficient selective uptake, despite high affinity HDL binding. To identify domain(s) of SR-BI involved in selective lipid uptake, we designed seven SR-BI/CD36 chimeras in which distinct regions as defined by exon sequences were swapped between human SR-BI and mouse CD36. Three of these chimeric receptors (C2, C4, and C6) were successfully expressed in COS7 cells by transient transfection and studied for functional activity. The other chimeric proteins were not expressed to detectable levels in COS cells. Chimeric receptors containing substitutions of certain regions in SR-BI with the corresponding domains of CD36 retained high affinity binding of HDL, but were defective in selective uptake. Our results suggest that multiple non contiguous domains on SR-BI may mediate HDL interaction. Interestingly, C4 mediated similar oxLDL binding, but &sim;5 fold lower HDL binding, compared to wild type SR-BI, suggesting that distinct sites on SR-BI are involved in HDL and oxLDL binding.
520 $a Our studies provide new insight into the metabolism of oxLDL by SR-BI and CD36. Although SR-BI and CD36 bind oxLDL with similar high affinity, SR-BI mediates cellular oxLDL degradation less effectively than CD36. We investigated CD36 and SR-BI-mediated oxLDL internalization. COS-7 cells expressing exogenous CD36 or SR-BI were incubated with fluorescent-labeled oxLDL and the cellular distribution of oxLDL was monitored by confocal microscopy. We also quantified oxLDL internalization by CD36 and SR-BI using the fluorescence-based assay. The major findings of these studies were: (1) The intracellular trafficking of oxLDL in SR-BI- and CD36-expressing cells differs; (2) oxLDL uptake by SR-BI and CD36 is independent of caveolae, microtubules, and actin cytoskeleton, respectively; (3) Endocytosis of oxLDL by CD36, but not SR-BI, is dynamin 1-dependent. These studies indicate that distinct mechanisms are involved in oxLDL uptake and cellular trafficking by SR-BI and CD36.
590 $a School code: 0102.
650 4 $a Health Sciences, Nutrition. $3 1017801
690 $a 0570
710 2 0 $a University of Kentucky. $3 1017485
773 0 $t Dissertation Abstracts International $g 68-04B.
790 $a 0102
790 1 0 $a Van Der Westhuyzen, Deneys R., $e advisor
790 1 0 $a Webb, Nancy R., $e advisor
791 $a Ph.D.
792 $a 2006
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3259193