scholarly journals Scavenger Receptor BI-mediated Selective Uptake Is Required for the Remodeling of High Density Lipoprotein by Endothelial Lipase

2009 ◽  
Vol 284 (10) ◽  
pp. 6093-6100 ◽  
Author(s):  
Niels Nijstad ◽  
Harmen Wiersma ◽  
Thomas Gautier ◽  
Markus van der Giet ◽  
Cyrille Maugeais ◽  
...  
2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Alexandra C Chadwick ◽  
Rebecca L Holme ◽  
Paula-Dene C Nesbeth ◽  
Kirkwood A Pritchard ◽  
Daisy Sahoo

High density lipoprotein (HDL) combats atherosclerosis, largely through its role in the reverse cholesterol transport (RCT) pathway where excess cholesterol from peripheral tissues is transported by HDL to the liver for excretion. High HDL-cholesterol (HDL-C) levels have been traditionally linked to a lower risk for cardiovascular disease (CVD). However, recent evidence suggests that HDL “function”, rather than HDL levels, is a better indicator of CVD risk as modifications to HDL under oxidative stress can render the particles “dysfunctional”. Scavenger receptor BI (SR-BI), the HDL receptor, mediates the selective uptake of HDL-cholesteryl ester (CE) into the liver during RCT. We hypothesized that SR-BI would be unable to mediate its cholesterol transport functions in the presence of oxidized or modified HDL due to an inability to engage in productive binding interactions with modified ligands. To test this hypothesis, we assessed HDL binding and selective uptake of HDL-CE in COS7 cells transiently expressing SR-BI using native HDL or HDL modified with: 1) copper (Cu2+), 2) 4-hydroxynonenal (HNE), or 3) acrolein. Our data revealed that, compared to native HDL, SR-BI bound 20-50% less Cu2+-HDL and acrolein-HDL, and mediated 40%-60% less selective uptake of CE from these modified particles, respectively. On the other hand, while SR-BI was able to bind HNE-HDL, it could not efficiently mediate cholesterol uptake (20% less compared to native HDL). Interestingly, our data also revealed that the ability of SR-BI to mediate the release of free cholesterol from COS7 cells did not differ when modified HDL served as acceptor particles, as compared to native HDL. Taken together, only the HDL binding and HDL-CE selective uptake functions of SR-BI are influenced by the type of modification on the HDL particle. These data have significant implications as they suggest that higher levels of plasma HDL-C may, in part, be the result of the inability of SR-BI to recognize and mediate cholesterol removal from HDL particles that have been exposed to oxidative stress. More detailed investigations of the interactions between SR-BI and various populations of oxidized HDL will improve our understanding of the mechanisms that render HDL dysfunctional, and ultimately, atherogenic.


2004 ◽  
Vol 15 (1) ◽  
pp. 384-396 ◽  
Author(s):  
Yinan Peng ◽  
Wendy Akmentin ◽  
Margery A. Connelly ◽  
Sissel Lund-Katz ◽  
Michael C. Phillips ◽  
...  

Receptor-mediated trafficking of cholesterol between lipoproteins and cells is a fundamental biological process at the organismal and cellular levels. In contrast to the well-studied pathway of LDL receptor-mediated endocytosis, little is known about the trafficking of high-density lipoprotein (HDL) cholesterol by the HDL receptor, scavenger receptor BI (SR-BI). SR-BI mediates HDL cholesteryl ester uptake in a process in which HDL lipids are selectively transferred to the cell membrane without the uptake and degradation of the HDL particle. We report here the cell surface locale where the trafficking of HDL cholesterol occurs. Fluorescence confocal microscopy showed SR-BI in patches and small extensions of the cell surface that were distinct from sites of caveolin-1 expression. Electron microscopy showed SR-BI in patches or clusters primarily on microvillar extensions of the plasma membrane. The organization of SR-BI in this manner suggests that this microvillar domain is a way station for cholesterol trafficking between HDL and cells. The types of phospholipids in this domain are unknown, but SR-BI is not strongly associated with classical membrane rafts rich in detergent-resistant saturated phospholipids. We speculate that SR-BI is in a more fluid membrane domain that will favor rapid cholesterol flux between the membrane and HDL.


2014 ◽  
Vol 34 (5) ◽  
pp. 966-975 ◽  
Author(s):  
Ling Guo ◽  
Zhong Zheng ◽  
Junting Ai ◽  
Deborah A. Howatt ◽  
Paul R. Mittelstadt ◽  
...  

1999 ◽  
Vol 274 (29) ◽  
pp. 20344-20350 ◽  
Author(s):  
Wendi V. Rodrigueza ◽  
Stephen T. Thuahnai ◽  
Ryan E. Temel ◽  
Sissel Lund-Katz ◽  
Michael C. Phillips ◽  
...  

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