In:
Arteriosclerosis, Thrombosis, and Vascular Biology, Ovid Technologies (Wolters Kluwer Health), Vol. 33, No. suppl_1 ( 2013-05)
Abstract:
Reverse cholesterol transport (RCT), the transfer of cholesterol from peripheral tissues, including the subendothelial space of the arterial wall, to the liver for disposal, is a current model of HDL atheroprotection. The final RCT step, selective hepatic HDL-cholesteryl ester (CE) uptake, is mediated by scavenger receptor class B type I (SR-BI). The net receptor reaction of SR-BI vs. HDL is distinct from that of LDL vs. the LDL receptor. LDL holo particle uptake is succeeded by steps that breakdown apo B-100 and hydrolyze and recycle the CE. In contrast, HDL-CE uptake is selective, occurring without a concomitant net uptake of the major HDL protein, apo A-I and even though apo E and apo A-I bind equally well to SR-BI, apoA-I-containing particles mediate 2-fold more selective CE uptake. The reaction of HDL with SR-BI is similar to the activity of a streptococcal serum opacity factor (SOF) against HDL_both reactions selectively remove CE from HDL leaving remnants. In addition, SOF catalyzes the displacement of apo A-I leaving an apo A-II-rich neo HDL, an effect that was assigned to the greater lipophilicity of apo A-II vs. apo A-I. Thus, we tested the hypothesis that the same occurs during the interaction of HDL with SR-BI, i.e., that apo A-II vs. apo A-I is selectively excluded from cellular uptake via SR-BI. Herein, we compare the selective uptake of HDL-CE vs. HDL-apo A-I and apo A-II. Cellular uptake of HDL-[ 3 H]CE labeled with [ 125 I]apo A-I or [ 125 I]apo A-II was compared in CHO-K1 and CHO-ldlA7 cells (LDL-R -/- ) with and without over expression of mouse SR-BI, and Huh7 human hepatocytes. Cell-associated 125 I and 3 H were determined by γ- and β-counting respectively. Uptake of CE, apo A-I, and apo A-II SR-BI-over expressing CHO cells was 32,800 ± 4800, 9.3 ± 2.7, and 2.5 ± 0.2 nmol/mg cell protein. The corresponding values for Huh7 cells were 9,700 ± 1,800, 15 ± 2.4, and 7.6 ± 0.9 nmol/mg cell protein. Relative to CE, both apo A-I and apo A-II were excluded from uptake by all cells. However, relative to the apo A-I and apo A-II contents of HDL, uptake of apo A-I was twice that of apo A-II, thus supporting the hypothesis that the more lipophilic apo A-II is selectively excluded from cellular uptake via SR-BI and retained in the neo HDL remnant.
Type of Medium:
Online Resource
ISSN:
1079-5642
,
1524-4636
DOI:
10.1161/atvb.33.suppl_1.A102
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2013
detail.hit.zdb_id:
1494427-3
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