Linked Life Data

11435418

Source:http://linkedlifedata.com/resource/pubmed/id/11435418

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
35
pubmed:dateCreated
2001-8-27
pubmed:abstractText
The reaction of lecithin:cholesterol acyltransferase (LCAT) with high density lipoproteins (HDL) is of critical importance in reverse cholesterol transport, but the structural and functional pathways involved in the regulation of LCAT have not been established. We present evidence for the direct binding of LCAT to alpha(2)-macroglobulin (alpha(2)M) in human plasma to form a complex 18.5 nm in diameter. Forty percent of plasma LCAT-HDL was associated with alpha(2)M; moreover, most of the LCAT in cerebrospinal fluid and in the medium of cultured human hepatoma cell line was associated with alpha(2)M. Purified recombinant human LCAT (rLCAT) labeled with (125)I bound to native and methylamine-activated alpha(2)M (alpha(2)M-MA) in vitro in a time- and concentration-dependent manner, and this binding did not depend on the presence of lipid. rLCAT bound to alpha(2)M-MA with greater affinity than to alpha(2)M. Furthermore, rLCAT did not activate alpha(2)M as phosphatidylcholine-specific phospholipase C does. Reconstituted HDL particles (LpA-I) inhibited the binding of rLCAT to alpha(2)M more efficiently than native HDL(3) did. LCAT associated with alpha(2)M was enzymatically inactive under both endogenous and exogenous assay conditions. Purified rLCAT alone did not bind to low density lipoprotein receptor-related protein (LRP) as lipoprotein lipase (LPL) does; however, when rLCAT was combined with alpha(2)M-MA to form a complex, binding, internalization, and degradation of rLCAT took place in LRP-expressing cells (LRP (+/+)) but not in cells deficient in LRP (LRP (-/-)). It is concluded that the binding of LCAT to alpha(2)M inhibits its enzymatic activity. Furthermore, the finding supports the possibility that the LRP receptor can act in vivo to mediate clearance of the LCAT-alpha(2)M complex and may significantly influence the bioavailability of LCAT.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
31
pubmed:volume
276
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
33241-8
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:11435418-Apolipoprotein E3, pubmed-meshheading:11435418-Apolipoproteins E, pubmed-meshheading:11435418-Binding Sites, pubmed-meshheading:11435418-Carcinoma, Hepatocellular, pubmed-meshheading:11435418-Genotype, pubmed-meshheading:11435418-Humans, pubmed-meshheading:11435418-Kinetics, pubmed-meshheading:11435418-Liver Neoplasms, pubmed-meshheading:11435418-Low Density Lipoprotein Receptor-Related Protein-1, pubmed-meshheading:11435418-Male, pubmed-meshheading:11435418-Phosphatidylcholine-Sterol O-Acyltransferase, pubmed-meshheading:11435418-Protein Binding, pubmed-meshheading:11435418-Receptors, Immunologic, pubmed-meshheading:11435418-Receptors, LDL, pubmed-meshheading:11435418-Recombinant Proteins, pubmed-meshheading:11435418-Tumor Cells, Cultured, pubmed-meshheading:11435418-Type C Phospholipases, pubmed-meshheading:11435418-alpha-Macroglobulins
pubmed:year
2001
pubmed:articleTitle
Interaction of lecithin:cholesterol acyltransferase (LCAT).alpha 2-macroglobulin complex with low density lipoprotein receptor-related protein (LRP). Evidence for an alpha 2-macroglobulin/LRP receptor-mediated system participating in LCAT clearance.
pubmed:affiliation
Cardiovascular Genetics Laboratory, McGill University Health Center/Royal Victoria Hospital, Montréal, Québec H3A 1A1, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't