scholarly journals Mechanism of cellular cholesterol removal: A communication system between extracellular cholesterol transport and intracellular cholesterol homeostasis.

1998 ◽  
Vol 111 (2) ◽  
pp. 77-85
Author(s):  
Shinji YOKOYAMA
Keyword(s):  
Communication System ◽  
Cholesterol Homeostasis ◽  
Cholesterol Transport ◽  
Cholesterol Removal ◽  
Cellular Cholesterol ◽  
Intracellular Cholesterol

Mechanisms for Cellular Cholesterol Transport: Defects and Human Disease

2006 ◽  
Vol 86 (4) ◽  
pp. 1237-1261 ◽  
Author(s):  
Elina Ikonen
Keyword(s):  
Mouse Models ◽  
Human Disease ◽  
Human Diseases ◽  
Cholesterol Transport ◽  
Cholesterol Trafficking ◽  
Cellular Cholesterol ◽  
Intracellular Cholesterol

This review summarizes the mechanisms of cellular cholesterol transport and monogenic human diseases caused by defects in intracellular cholesterol processing. In addition, selected mouse models of disturbed cholesterol trafficking are discussed. Current pharmacological strategies to prevent atherosclerosis are largely based on altering cellular cholesterol balance and are introduced in this context. Finally, because of the organizing potential of cholesterol in membranes, disturbances in cellular cholesterol transport have implications for a wide variety of human diseases, of which selected examples are given.

scholarly journals ABCA1 causes an asymmetric cholesterol distribution to regulate intracellular cholesterol homeostasis

2021 ◽  
Author(s):  
Fumihiko Ogasawara ◽  
Kazumitsu Ueda
Keyword(s):  
Endoplasmic Reticulum ◽  
Plasma Membrane ◽  
Cholesterol Level ◽  
Cholesterol Homeostasis ◽  
Contact Site ◽  
Cell Plasma Membrane ◽  
Cellular Cholesterol ◽  
Outer Leaflet ◽  
Cell Plasma ◽  
Intracellular Cholesterol

AbstractCholesterol is a major and essential component of the mammalian cell plasma membrane (PM) and the loss of cholesterol homeostasis leads to various pathologies. Cellular cholesterol uptake and synthesis are regulated by a cholesterol sensor in the endoplasmic reticulum (ER). However, it remains unclear how the PM cholesterol level is sensed. Here we show that the sensing depends on ATP-binding cassette A1 (ABCA1) and Aster-A, which cooperatively maintain the asymmetric transbilayer cholesterol distribution in the PM. ABCA1 translocates (flops) cholesterol from the inner to the outer leaflet of the PM to maintain a low inner cholesterol level. When the inner cholesterol level exceeds a threshold, Aster-A is recruited to the PM-ER contact site to transfer cholesterol to the ER. These results show unknown synergy between ABCA1 and Aster-A in intracellular cholesterol homeostasis.

scholarly journals Increased concentration of 7-ketocholesterol and 7β-hydroxycholesterol in HDL from young anabolic androgenic steroid users

2020 ◽  
Author(s):  
Francis Souza ◽  
Marcelo Santos ◽  
Guilherme Fonseca ◽  
Guilherme Ferreira ◽  
Carlos Negrão ◽  
...  
Keyword(s):  
Cholesterol Homeostasis ◽  
Gas Chromatography Mass Spectrometry ◽  
Cholesterol Transport ◽  
Anabolic Androgenic Steroid ◽  
Cholesterol Removal ◽  
Cross Sectional ◽  
Lower Ability ◽  
Mediate Cell ◽  
Androgenic Steroids

Abstract Background:Oxysterols are cholesterol oxidative derivatives that play an important role in cell cholesterol homeostasis. However, HDL particles enriched with oxysterols, especially the 7-ketocholesterol, have lower ability to mediate cell cholesterol removal by the reverse cholesterol transport. Anabolic androgenic steroids (AAS) misuse is associated with diminished cholesterol efflux and increased atherogenesis in young men. Unknown is whether the concentration of oxysterols is altered in AAS users.Methods:In this subanalysis, we evaluated six AAS users (AASU) and 6 AAS nonusers (AASNU) involved in strength training, and 6 sedentary men (SC). Oxysterols were evaluated by gas chromatography-mass spectrometry in HDL particles isolated by ultra centrifugation.Results:AASU presented higher levels of 7-ketocholesterol (104.1 ± 64.0 vs.43.7 ± 8.3 and 43.2 ± 9.1 ng/mg C; p < 0.05) and 7β-hydroxycholesterol (15.5 ± 5.6 vs. 10.1 ± 2.0 and 8.1 ± 1.0 ng/mg C; p < 0.05) in HDL compared to AASNU and SC, respectively. 7α-hydroxycholesterol (10.7 ± 4.2 vs. 8.0 ± 1.5 and 6.8 ± 2.2 ng/mg C; p = 0.089) and 27 hydroxycholesterol (25.6 ± 7.2 vs. 28.0 ± 7.0 and 21.8 ± 3.2 ng/mg C; p = 0.235) were similar among groups.Conclusion:This pilot study suggests that AAS abuse increases 7-ketocholesterol and 7β-hydroxycholesterol in HDL that may be related to HDL impaired function and increased atherosclerotic coronary disease in young AAS users. The clinical implication of this finding should be considered in future, larger, long-term studies.Trial registration:This is a cross-sectional pilot observational study from a retrospectively registered study NCT03450837.

Caveolin-1 and regulation of cellular cholesterol homeostasis

2006 ◽  
Vol 291 (2) ◽  
pp. H677-H686 ◽  
Author(s):  
Philippe G. Frank ◽  
Michelle W.-C. Cheung ◽  
Stephanos Pavlides ◽  
Gemma Llaverias ◽  
David S. Park ◽  
...  
Keyword(s):  
Cholesterol Efflux ◽  
Free Cholesterol ◽  
Scavenger Receptor ◽  
Cholesterol Homeostasis ◽  
Type I ◽  
Wild Type ◽  
Cellular Cholesterol ◽  
Caveolin 1 ◽  
Intracellular Cholesterol ◽  
Cellular Cholesterol Efflux

Caveolae are 50- to 100-nm cell surface plasma membrane invaginations present in terminally differentiated cells. They are characterized by the presence of caveolin-1, sphingolipids, and cholesterol. Caveolin-1 is thought to play an important role in the regulation of cellular cholesterol homeostasis, a process that needs to be properly controlled to limit and prevent cholesterol accumulation and eventually atherosclerosis. We have recently generated caveolin-1-deficient [Cav-1(−/−)] mice in which caveolae organelles are completely eliminated from all cell types, except cardiac and skeletal muscle. In the present study, we examined the metabolism of cholesterol in wild-type (WT) and Cav-1(−/−) mouse embryonic fibroblasts (MEFs) and mouse peritoneal macrophages (MPMs). We observed that Cav-1(−/−) MEFs are enriched in esterified cholesterol but depleted of free cholesterol compared with their wild-type counterparts. Similarly, Cav-1(−/−) MPMs also contained less free cholesterol and were enriched in esterified cholesterol on cholesterol loading. In agreement with this finding, caveolin-1 deficiency was associated with reduced free cholesterol synthesis but increased acyl-CoA:cholesterol acyl-transferase (ACAT) activity. In wild-type MPMs, we observed that caveolin-1 was markedly upregulated on cholesterol loading. Despite these differences, cellular cholesterol efflux from MEFs and MPMs to HDL was not affected in the Cav-1-deficient cells. Neither ATP-binding cassette transporter G1 (ABCG1)- nor scavenger receptor class B type I (SR-BI)-mediated cholesterol efflux was affected. Cellular cholesterol efflux to apolipoprotein A-I was not significantly reduced in Cav-1(−/−) MPMs compared with wild-type MPMs. However, ABCA1-mediated cholesterol efflux was clearly more sensitive to the inhibitory effects of glyburide in Cav-1(−/−) MPMs versus WT MPMs. Taken together, these findings suggest that caveolin-1 plays an important role in the regulation of intracellular cholesterol homeostasis and can modulate the activity of other proteins that are involved in the regulation of intracellular cholesterol homeostasis.

scholarly journals The reverse cholesterol transport system as a potential mediator of luteolysis in the primate corpus luteum

Reproduction ◽  
2010 ◽  
Vol 139 (1) ◽  
pp. 163-176 ◽  
Author(s):  
Randy L Bogan ◽  
Jon D Hennebold
Keyword(s):  
Corpus Luteum ◽  
Reverse Cholesterol Transport ◽  
Density Lipoprotein ◽  
Cholesterol Homeostasis ◽  
Cholesterol Transport ◽  
Functional Regression ◽  
Lipoprotein Receptors ◽  
Cholesterol Uptake ◽  
Genes Encoding ◽  
Intracellular Cholesterol

The cessation of progesterone (P4) production (i.e. functional regression), arguably the key event in luteolysis of the primate corpus luteum (CL), is poorly understood. Previously, we found that genes encoding proteins involved in cholesterol uptake decreased, while those involved in cholesterol efflux (reverse cholesterol transport, RCT) increased in expression during spontaneous functional regression of the rhesus macaque CL, thereby potentially depleting the cholesterol reserves needed for steroidogenesis. Therefore, a comprehensive analysis of the components necessary for RCT was performed. RCT components were expressed (mRNA and/or protein) in the macaque CL including cholesterol sensors (liver X receptors α or NR1H3; and β or NR1H2), efflux proteins (ATP-binding cassette subfamilies A1 (ABCA1) and G1), acceptors (apolipoproteins A1 or APOA1; and E or APOE), and plasma proteins facilitating high-density lipoprotein formation (lecithin:cholesterol acyltransferase or LCAT; phospholipid transfer protein or PLTP). ABCA1, APOE, PLTP, and NR1H3 increased, while lipoprotein receptors decreased, in expression (mRNA and/or protein) through the period of functional regression. The expression ofAPOA1andAPOE, as well asNR1H3, was greatest in the CL and tissues involved in regulating cholesterol homeostasis. Immunolocalization studies revealed that RCT proteins and lipoprotein receptors were expressed in large luteal cells, which possess intracellular cholesterol reserves during periods of P4synthesis. Lipid staining revealed changes in luteal cholesterol ester/lipid distribution that occurred following functional regression. These results indicate that decreased cholesterol uptake and increased RCT may be critical for the initiation of primate luteolysis by limiting intracellular cholesterol pools required for steroidogenesis.

scholarly journals Modulation of Cellular Cholesterol Transport and Homeostasis by Rab11

2002 ◽  
Vol 13 (9) ◽  
pp. 3107-3122 ◽  
Author(s):  
Maarit Hölttä-Vuori ◽  
Kimmo Tanhuanpää ◽  
Wiebke Möbius ◽  
Pentti Somerharju ◽  
Elina Ikonen
Keyword(s):  
Plasma Membrane ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Cholesterol Homeostasis ◽  
Cholesterol Transport ◽  
Rab Proteins ◽  
Independent Manner ◽  
Cellular Cholesterol ◽  
Gm2 Ganglioside ◽  
Recycling Endosomes

To analyze the contribution of vesicular trafficking pathways in cellular cholesterol transport we examined the effects of selected endosomal Rab proteins on cholesterol distribution by filipin staining. Transient overexpression of Rab11 resulted in prominent accumulation of free cholesterol in Rab11-positive organelles that sequestered transferrin receptors and internalized transferrin. Sphingolipids were selectively redistributed as pyrene-sphingomyelin and sulfatide cosequestered with Rab11-positive endosomes, whereas globotriaosyl ceramide and GM2 ganglioside did not. Rab11 overexpression did not perturb the transport of 1,1′-dioctadecyl-3,3,3′,3′-tetramethyl-indocarbocyanine-perchlorate–labeled low-density lipoprotein (LDL) to late endosomes or the Niemann-Pick type C1 (NPC1)-induced late endosomal cholesterol clearance in NPC patient cells. However, Rab11 overexpression inhibited cellular cholesterol esterification in an LDL-independent manner. This effect could be overcome by introducing cholesterol to the plasma membrane by using cyclodextrin as a carrier. These results suggest that in Rab11-overexpressing cells, deposition of cholesterol in recycling endosomes results in its impaired esterification, presumably due to defective recycling of cholesterol to the plasma membrane. The findings point to the importance of the recycling endosomes in regulating cholesterol and sphingolipid trafficking and cellular cholesterol homeostasis.

Modulation of intestinal cholesterol absorption by high glucose levels: impact on cholesterol transporters, regulatory enzymes, and transcription factors

2008 ◽  
Vol 295 (5) ◽  
pp. G873-G885 ◽  
Author(s):  
Z. Ravid ◽  
M. Bendayan ◽  
E. Delvin ◽  
A. T. Sane ◽  
M. Elchebly ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Protein Expression ◽  
High Glucose ◽  
Cholesterol Absorption ◽  
Cholesterol Homeostasis ◽  
Cholesterol Transport ◽  
Intestinal Cholesterol Absorption ◽  
Cholesterol Uptake ◽  
Glucose Levels

Growing evidence suggests that the small intestine may contribute to excessive postprandial lipemia, which is highly prevalent in insulin-resistant/Type 2 diabetic individuals and substantially increases the risk of cardiovascular disease. The aim of the present study was to determine the role of high glucose levels on intestinal cholesterol absorption, cholesterol transporter expression, enzymes controlling cholesterol homeostasis, and the status of transcription factors. To this end, we employed highly differentiated and polarized cells (20 days of culture), plated on permeable polycarbonate filters. In the presence of [14C]cholesterol, glucose at 25 mM stimulated cholesterol uptake compared with Caco-2/15 cells supplemented with 5 mM glucose ( P < 0.04). Because combination of 5 mM glucose with 20 mM of the structurally related mannitol or sorbitol did not change cholesterol uptake, we conclude that extracellular glucose concentration is uniquely involved in the regulation of intestinal cholesterol transport. The high concentration of glucose enhanced the protein expression of the critical cholesterol transporter NPC1L1 and that of CD36 ( P < 0.02) and concomitantly decreased SR-BI protein mass ( P < 0.02). No significant changes were observed in the protein expression of ABCA1 and ABCG8, which act as efflux pumps favoring cholesterol export out of absorptive cells. At the same time, 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity was decreased ( P < 0.007), whereas ACAT activity remained unchanged. Finally, increases were noted in the transcription factors LXR-α, LXR-β, PPAR-β, and PPAR-γ along with a drop in the protein expression of SREBP-2. Collectively, our data indicate that glucose at high concentrations may regulate intestinal cholesterol transport and metabolism in Caco-2/15 cells, thus suggesting a potential influence on the cholesterol absorption process in Type 2 diabetes.

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