scholarly journals Scavenger receptor BI and ABCG5/G8 differentially impact biliary sterol secretion and reverse cholesterol transport in mice

Hepatology ◽  
2013 ◽  
Vol 58 (1) ◽  
pp. 293-303 ◽  
Author(s):  
Arne Dikkers ◽  
Jan Freak de Boer ◽  
Wijtske Annema ◽  
Albert K. Groen ◽  
Uwe J.F. Tietge
Keyword(s):  
Reverse Cholesterol Transport ◽  
Scavenger Receptor ◽  
Cholesterol Transport ◽  
Scavenger Receptor Bi

scholarly journals Proline residues in scavenger receptor-BI's C-terminal region support efficient cholesterol transport

2019 ◽  
Vol 476 (6) ◽  
pp. 951-963
Author(s):  
Sarah C. Proudfoot ◽  
Daisy Sahoo
Keyword(s):  
Reverse Cholesterol Transport ◽  
Transmembrane Domain ◽  
Scavenger Receptor ◽  
Resonance Structure ◽  
High Density Lipoproteins ◽  
Cholesterol Transport ◽  
Nuclear Magnetic Resonance Structure ◽  
Scavenger Receptor Bi ◽  
High Affinity Receptor ◽  
Mutant Receptors

Abstract High-density lipoproteins (HDLs) facilitate reverse cholesterol transport, a process in which HDL removes cholesterol from circulation and carries it to the liver for biliary excretion. Reverse cholesterol transport is also facilitated by HDL's high-affinity receptor, scavenger receptor-BI (SR-BI), by mechanisms that are not fully understood. To improve our understanding of SR-BI function, we previously solved the NMR (nuclear magnetic resonance) structure of a peptide encompassing amino acids 405–475 of SR-BI. This segment of SR-BI, that includes the functionally critical C-terminal transmembrane domain and part of the extracellular domain, also contains four conserved proline (Pro) residues. We hypothesized that these proline residues support SR-BI in a conformation that allows for efficient cholesterol transport. To test this, we generated individual Pro-to-alanine mutations in full-length SR-BI and transiently expressed the mutant receptors in COS-7 cells to measure the effects on SR-BI-mediated cholesterol transport functions. Our findings reveal that HDL cell association and uptake of HDL-cholesteryl esters are impaired by mutation of Pro-412, Pro-438, or the transmembrane proline kink residue (Pro-459). In addition, SR-BI-mediated cholesterol efflux and membrane cholesterol distribution are impaired by mutation of Pro-412 or Pro-438, indicating that these residues are essential for a fully functional SR-BI receptor. Furthermore, we demonstrate that Pro-408 is necessary for proper SR-BI expression, but mutation of Pro-408 does not cause SR-BI to become misfolded or rapidly degraded by the proteasome or the lysosome. We conclude that key proline residues play an important role in SR-BI function by allowing for the efficient transport of cholesterol between cells and HDL.

scholarly journals Apolipoprotein A1-Related Proteins and Reverse Cholesterol Transport in Antiatherosclerosis Therapy: Recent Progress and Future Perspectives

2022 ◽  
Vol 2022 ◽  
pp. 1-9
Author(s):  
Xiuting Xu ◽  
Zikai Song ◽  
Bao Mao ◽  
Guoliang Xu
Keyword(s):  
Reverse Cholesterol Transport ◽  
Scavenger Receptor ◽  
Cholesterol Acyltransferase ◽  
Density Lipoprotein ◽  
Coronary Artery Occlusion ◽  
Artery Occlusion ◽  
The Body ◽  
Apolipoprotein A1 ◽  
Cholesterol Transport ◽  
Class B

Hyperlipidemia characterized by abnormal deposition of cholesterol in arteries can cause atherosclerosis and coronary artery occlusion, leading to atherosclerotic coronary heart disease. The body prevents atherosclerosis by reverse cholesterol transport to mobilize and excrete cholesterol and other lipids. Apolipoprotein A1, the major component of high-density lipoprotein, plays a key role in reverse cholesterol transport. Here, we reviewed the role of apolipoprotein A1-targeting molecules in antiatherosclerosis therapy, in particular ATP-binding cassette transporter A1, lecithin-cholesterol acyltransferase, and scavenger receptor class B type 1.

Abstract 404: Altered Interaction of Modified High Density Lipoprotein with Scavenger Receptor BI

2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Alexandra C Chadwick ◽  
Rebecca L Holme ◽  
Paula-Dene C Nesbeth ◽  
Kirkwood A Pritchard ◽  
Daisy Sahoo
Keyword(s):  
Oxidative Stress ◽  
High Density Lipoprotein ◽  
Scavenger Receptor ◽  
Density Lipoprotein ◽  
High Density ◽  
Cholesterol Transport ◽  
Selective Uptake ◽  
Peripheral Tissues ◽  
Scavenger Receptor Bi ◽  
Hdl Function

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.

scholarly journals Effects of Astaxanthin on Reverse Cholesterol Transport and Atherosclerosis in Mice

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Tang-Bin Zou ◽  
Shan-Shan Zhu ◽  
Fei Luo ◽  
Wei-Qiao Li ◽  
Xue-Rong Sun ◽  
...  
Keyword(s):  
Reverse Cholesterol Transport ◽  
Scavenger Receptor ◽  
Hdl Cholesterol ◽  
High Plasma ◽  
Cholesterol Transport ◽  
Atp Binding ◽  
Type I ◽  
Aortic Sinus ◽  
Atp Binding Cassette Transporter ◽  
Atp Binding Cassette

High plasma level of HDL-cholesterol (HDL-C) has been consistently associated with a decreased risk of atherosclerosis (AS); thus, HDL-C is considered to be an antiatherogenic lipoprotein. The development of novel therapies to enhance the atheroprotective properties of HDL may have the possibility of further reducing the residual AS risk. Reverse cholesterol transport (RCT) is believed to be a primary atheroprotective activity of HDL, which has been shown to promote the efflux of excess cholesterol from macrophage-derived foam cells via ATP-binding cassette transporter A1 (ABCA1), ATP-binding cassette transporter G1 (ABCG1), and scavenger receptor class B type I (SR-BI) and then transport it back to the liver for excretion into bile and eventually into the feces. In the current study, we investigated the effects of astaxanthin on RCT and AS progression in mice. The results showed that short- and long-term supplementation of astaxanthin promote RCT in C57BL/6J and ApoE−/−mice, respectively. Moreover, astaxanthin can relieve the plaque area of the aortic sinus and aortic cholesterol in mice. These findings suggest that astaxanthin is beneficial for boosting RCT and preventing the development of AS.

scholarly journals HDL mediates reverse cholesterol transport from ram spermatozoa and induces hyperactivated motility

2021 ◽  
Author(s):  
Naomi C Bernecic ◽  
Simon P Graaf ◽  
Tamara Leahy ◽  
Bart M Gadella
Keyword(s):  
Reverse Cholesterol Transport ◽  
Cholesterol Efflux ◽  
Scavenger Receptor ◽  
High Density Lipoproteins ◽  
In Vitro Fertilisation ◽  
Critical Event ◽  
Cholesterol Transport ◽  
Type I

ABSTRACT Reverse Cholesterol Transport or cholesterol efflux is part of an extensive plasma membrane remodelling process in spermatozoa that is imperative for fertilisation. For ram spermatozoa, sheep serum is well known to support in vitro fertilisation (IVF), but knowledge of its explicit role is limited. Though, it is postulated to elicit cholesterol efflux owing to the presence of high density lipoproteins (HDLs) that interact with transmembrane cholesterol transporters, such as ATP-binding cassette transporter A1 (ABCA1) and scavenger receptor class B, type I (SR-BI). In this study, we report that both sheep serum and HDLs were able to elicit cholesterol efflux alone by up to 20–40% (as measured by the BODIPY-cholesterol assay). Furthermore, when the antagonists glibenclamide and valspodar were used to inhibit the function of ABCA1 and SR-BI or ABCA1 alone, respectively, cholesterol efflux was only marginally reduced (8–15)%. Nevertheless, it is likely that in ram spermatozoa, a specific facilitated pathway of cholesterol efflux is involved in the interaction between cholesterol acceptors and transporters. Interestingly, exposure to HDLs also induced hyperactivated motility, another critical event required for successful fertilisation. Taken together, this study details the first report of the dual action of HDLs on ram spermatozoa, providing both an insight into the intricacy of events leading up to fertilisation in vivo as well as demonstrating the possible application of HDL supplementation in media for IVF.

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