Linked Life Data

12746448

Source:http://linkedlifedata.com/resource/pubmed/id/12746448

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
31
pubmed:dateCreated
2003-7-28
pubmed:abstractText
Autosomal recessive hypercholesterolemia (ARH) is a genetic form of hypercholesterolemia that clinically resembles familial hypercholesterolemia (FH). As in FH, the rate of clearance of circulating low density lipoprotein (LDL) by the LDL receptor (LDLR) in the liver is markedly reduced in ARH. Unlike FH, LDL uptake in cultured fibroblasts from ARH patients is normal or only slightly impaired. The gene defective in ARH encodes a putative adaptor protein that has been implicated in linking the LDLR to the endocytic machinery. To determine the role of ARH in the liver, ARH-deficient mice were developed. Plasma levels of LDL-cholesterol were elevated in the chow-fed Arh-/- mice (83 +/- 8 mg/dl versus 68 +/- 8 mg/dl) but were lower than those of mice expressing no LDLR (Ldlr-/-) (197 +/- 8 mg/dl). Cholesterol feeding elevated plasma cholesterol levels in both strains. The fractional clearance rate of radiolabeled LDL was reduced to similar levels in the Arh-/- and Ldlr-/- mice, whereas the rate of removal of alpha2-macroglobulin by the LDLR-related protein, which also interacts with ARH, was unchanged. Immunolocalization studies revealed that a much greater proportion of immunodetectable LDLR, but not LDLR-related protein, was present on the sinusoidal surface of hepatocytes in the Arh-/- mice. Taken together, these results are consistent with ARH playing a critical and specific role in LDLR endocytosis in the liver.
pubmed:grant
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
1
pubmed:volume
278
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
29024-30
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:12746448-Adaptor Proteins, Signal Transducing, pubmed-meshheading:12746448-Adaptor Proteins, Vesicular Transport, pubmed-meshheading:12746448-Animals, pubmed-meshheading:12746448-Centrifugation, Density Gradient, pubmed-meshheading:12746448-Cholesterol, pubmed-meshheading:12746448-Cholesterol, Dietary, pubmed-meshheading:12746448-Cholesterol, LDL, pubmed-meshheading:12746448-Endocytosis, pubmed-meshheading:12746448-Hypercholesterolemia, pubmed-meshheading:12746448-Hyperlipoproteinemia Type II, pubmed-meshheading:12746448-Iodine Radioisotopes, pubmed-meshheading:12746448-Lipoproteins, LDL, pubmed-meshheading:12746448-Liver, pubmed-meshheading:12746448-Metabolic Clearance Rate, pubmed-meshheading:12746448-Mice, pubmed-meshheading:12746448-Mice, Knockout, pubmed-meshheading:12746448-Receptors, LDL
pubmed:year
2003
pubmed:articleTitle
Normal sorting but defective endocytosis of the low density lipoprotein receptor in mice with autosomal recessive hypercholesterolemia.
pubmed:affiliation
Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9046, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't