Linked Life Data

8662777

Source:http://linkedlifedata.com/resource/pubmed/id/8662777

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
23
pubmed:dateCreated
1996-8-26
pubmed:abstractText
The stimulation of the intracellular cholesterol esterification pathway by atherogenic lipoproteins in macrophages is a key step in the development of atheroma foam cells. The esterification pathway can also be stimulated by hydrolysis of cell-surface sphingomyelin by the enzyme sphingomyelinase (SMase). In both cases, intracellular cholesterol transport to the cholesterol esterifying enzyme, acyl-CoA:cholesterol O-acyltransferase (ACAT), is thought to be critical, although the mechanism of cholesterol transport is not known. In this report, we explore two fundamental properties of the cholesterol esterification pathway, namely its dependence on energy and the effect of other treatments that block membrane vesicle trafficking. After the atherogenic lipoprotein, beta-very low density lipoprotein (beta-VLDL), was internalized by macrophages and hydrolyzed in lysosomes, the cells were depleted of energy by treatment with sodium azide and 2-deoxyglucose or by permeabilization. Under these conditions, which allowed equal beta-VLDL-cholesteryl ester hydrolysis, cholesterol esterification was markedly decreased in the energy-depleted cells. This effect was not due to blockage of lysosomal cholesterol export. In the permeabilized cell system, energy repletion restored beta-VLDL-induced cholesterol esterification. Remarkably, stimulation of cholesterol esterification by SMase was not inhibited by energy depletion. Energy depletion also inhibited beta-VLDL-induced, but not SMase-induced, cholesterol esterification in Chinese hamster ovary cells. Similar experiments were carried out using N-ethylmaleimide, low potassium medium, or inhibitors of phosphatidylinositol 3-kinase, each of which blocks intracellular membrane vesicle trafficking. These treatments also inhibited beta-VLDL-induced, but not SMase-induced, cholesterol esterification. Finally, we show here that SMase treatment of cells leads to an increase in plasma membrane vesiculation that is relatively resistant to energy depletion. In summary, the stimulation of cholesterol esterification by lipoproteins, but not by SMase, is energy-dependent, N-ethylmaleimide-sensitive, and blocked by both low potassium and phosphatidylinositol 3-kinase inhibitors. The affected step or steps are distal to cholesterol export from lysosomes and not due to direct inhibition of the ACAT enzyme. Thus, the mechanisms involved in lipoprotein-induced versus SMase-induced cholesterol esterification are different, perhaps due to the involvement of energy-dependent vesicular cholesterol transport in the lipoprotein pathway and a novel, energy-independent vesicular transport mechanism in the SMase pathway.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
7
pubmed:volume
271
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
13392-400
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:8662777-Animals, pubmed-meshheading:8662777-Biological Transport, Active, pubmed-meshheading:8662777-CHO Cells, pubmed-meshheading:8662777-Cell Line, pubmed-meshheading:8662777-Cholesterol, pubmed-meshheading:8662777-Cholesterol Esters, pubmed-meshheading:8662777-Cricetinae, pubmed-meshheading:8662777-Energy Metabolism, pubmed-meshheading:8662777-Enzyme Inhibitors, pubmed-meshheading:8662777-Esterification, pubmed-meshheading:8662777-Ethylmaleimide, pubmed-meshheading:8662777-Lipoproteins, pubmed-meshheading:8662777-Lipoproteins, VLDL, pubmed-meshheading:8662777-Lysosomes, pubmed-meshheading:8662777-Macrophages, pubmed-meshheading:8662777-Phosphatidylinositol 3-Kinases, pubmed-meshheading:8662777-Phosphotransferases (Alcohol Group Acceptor), pubmed-meshheading:8662777-Sphingomyelin Phosphodiesterase, pubmed-meshheading:8662777-Sterol O-Acyltransferase
pubmed:year
1996
pubmed:articleTitle
The distal pathway of lipoprotein-induced cholesterol esterification, but not sphingomyelinase-induced cholesterol esterification, is energy-dependent.
pubmed:affiliation
Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't