scholarly journals Effect of Cupric Ion on Cholesteryl Ester Hydrolysis in Rat Peritoneal Macrophages.

1993 ◽  
Vol 16 (2) ◽  
pp. 125-127 ◽  
Author(s):  
Mitsuo TANAKA
1990 ◽  
Vol 111 (3) ◽  
pp. 929-940 ◽  
Author(s):  
I Tabas ◽  
S Lim ◽  
X X Xu ◽  
F R Maxfield

Hypercholesterolemic rabbit beta-VLDL and human LDL are both internalized by mouse peritoneal macrophages by receptor-mediated endocytosis. However, only beta-VLDL (which binds to the cells with a much higher affinity than LDL) markedly stimulates acyl-CoA/cholesterol acyl transferase (ACAT) and induces foam cell formation in these cells. As an initial step to test whether the two lipoproteins might be targeted to different organelles (which might differ in their ability to deliver cholesterol to microsomal ACAT), we studied the endocytic pathways of beta-VLDL and LDL. Lipoproteins were labeled with the non-transferable fluorescent label, DiI. When the macrophages were incubated with DiI-LDL for 10 min at 37 degrees C, the fluorescence was concentrated near the center of the cell both in heavily labeled vesicles and in a diffuse pattern. The pattern with DiI-beta-VLDL was quite different: an array of bright vesicles throughout the cytoplasm was the predominant feature. Differences in distribution were seen as early as 2 min of incubation and persisted throughout a 10-min chase period. By using a procedure in which photobleaching of DiI fluorescence converts diaminobenzidine into an electron-dense marker, we were able to identify at the ultrastructural level vesicles containing electron-dense material in cells incubated with DiI-beta-VLDL. Human E2/E2 beta-VLDL (from a patient with familial dysbetalipoproteinemia), which has a binding affinity and ACAT-stimulatory potential similar to LDL, gave a pattern of fluorescence virtually identical to LDL. Pulse-chase studies with 125I-labeled and [3H]cholesteryl ester-labeled lipoproteins disclosed that both protein degradation and cholesteryl ester hydrolysis were markedly retarded in beta-VLDL compared with LDL. Thus, in mouse peritoneal macrophages, endocytosed beta-VLDL appears in a distinct set of widely-distributed vesicles not seen with LDL (or with E2-beta-VLDL) and, compared with LDL, has a markedly diminished rate of protein degradation and cholesteryl ester hydrolysis. The differential routing of LDL and beta-VLDL may provide a mechanism for differences in ACAT-stimulatory potential between the two lipoproteins.


2008 ◽  
Vol 28 (6) ◽  
pp. 1144-1150 ◽  
Author(s):  
Mireille Ouimet ◽  
Ming-Dong Wang ◽  
Natalie Cadotte ◽  
Kenneth Ho ◽  
Yves L. Marcel

1984 ◽  
Vol 99 (4) ◽  
pp. 1266-1274 ◽  
Author(s):  
D J Falcone ◽  
N Mated ◽  
H Shio ◽  
C R Minick ◽  
S D Fowler

The sequestration of low-density lipoprotein (LDL) by components of the vascular extracellular matrix has long been recognized as a contributing factor to lipid accumulation during atherogenesis. The effects, however, that components of the extracellular matrix might have on LDL catabolism by scavenger cells have been little investigated. For these purposes we have prepared insoluble complexes of LDL, heparin, fibronectin, and denatured collagen (gelatin) and examined their effects on lipid accumulation, LDL uptake and degradation, and cholesteryl ester synthesis in mouse peritoneal macrophages. The results of these experiments have demonstrated that the cholesteryl ester content of macrophages incubated with a particular suspension of LDL, heparin, fibronectin, and collagen complexes is four- to fivefold that of cells incubated with LDL alone. The uptake of complexes containing 125I-LDL is rapid; however, in contrast to either endocytosed 125I-LDL or 125I-acetyl LDL, the degradation of complex-derived LDL is impaired. In addition, the uptake of complex-derived LDL stimulates the incorporation of [14C]oleic acid into cholesteryl oleate, however, the stimulation was a small fraction of that observed in cells incubated with acetyl LDL. Ultrastructurally, macrophages incubated with LDL, heparin, fibronectin, and collagen complexes did not contain many lipid droplets, but rather their cytoplasm is filled with phagosomes containing material similar in appearance to LDL-matrix complexes. These results indicate that components of the extracellular matrix can alter the catabolism of LDL by scavenger cells, suggesting that they may play a role in cellular lipid accumulation in the atherosclerotic lesion.


2002 ◽  
Vol 44 (2) ◽  
pp. 331-341 ◽  
Author(s):  
Margery A. Connelly ◽  
Ginny Kellner-Weibel ◽  
George H. Rothblat ◽  
David L. Williams

2000 ◽  
Vol 149 (2) ◽  
pp. 343-350 ◽  
Author(s):  
Rachel A Harte ◽  
Lillemor M Hultén ◽  
Helena Lindmark ◽  
Karen Reue ◽  
Michael C Schotz ◽  
...  

2008 ◽  
Vol 49 (8) ◽  
pp. 1829-1838 ◽  
Author(s):  
Motohiro Sekiya ◽  
Jun-ichi Osuga ◽  
Naoya Yahagi ◽  
Hiroaki Okazaki ◽  
Yoshiaki Tamura ◽  
...  

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