Abstract：
:Two novel mutations of the low density lipoprotein (LDL)-receptor gene were found in two Italian familial hypercholesterolemia (FH)-heterozygotes. The first mutation was an 18 nucleotide duplication in exon 8 which is preceded by an A-->T transversion. The translation product of the mutant allele was predicted to be a receptor with an in-frame insertion of 6 amino acids in repeat B of the epidermal growth factor precursor homology domain. Analysis of LDL-receptor activity in the proband's fibroblasts showed a 50% reduction of 125I-labeled LDL binding and pulse-chase studies suggested that little, if any, of the mutant protein was processed to the mature form. The second mutation was a 7 kb duplication (from intron 2 to intron 6) of exons 3 through 6, predicted to encode an elongated receptor with the duplication of repeats 2-7 of the ligand binding domain. The elongated receptor was processed slightly more slowly than the normal receptor, but was converted to a mature form of the expected size. This mature, mutant receptor was degraded more rapidly than the normal receptor. On ligand blotting the elongated receptor bound twice as much LDL or beta-very low density lipoprotein (betaVLDL) as the normal receptor. In contrast, maximum binding of LDL to proband's cells was decreased to approximately 70% of the normal cells with a significant increase in apparent affinity. Cell association at 37 degrees C, internalization, and degradation showed a similar reduced maximum. Thus these mutations demonstrate that duplications of amino acid sequences in the low density lipoprotein LDL-receptor may disrupt the LDL-receptor pathway at different levels.
journal_name
J Lipid Resjournal_title
Journal of lipid researchauthors
Patel DD,Lelli N,Garuti R,Li Volti S,Bertolini S,Knight BL,Calandra Ssubject
Has Abstractpub_date
1998-07-01 00:00:00pages
1466-75issue
7eissn
0022-2275issn
1539-7262journal_volume
39pub_type
杂志文章abstract：:Clock genes respond to external stimuli and exhibit circadian rhythms. This study investigated the expression of clock genes in the small intestine and their contribution in the regulation of nutrient absorption by enterocytes. We examined expression of clock genes and macronutrient transport proteins in the small int...
journal_title：Journal of lipid research
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abstract：:Zinc Finger Protein 202 (ZNF202) is a transcriptional repressor that binds elements found predominantly in genes involved in HDL metabolism. We tested the following hypotheses: 1) frequencies of single-nucleotide polymorphisms (SNPs) and haplotypes in ZNF202 differ between individuals with low and high HDL cholesterol...
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journal_title：Journal of lipid research
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更新日期：2001-02-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
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更新日期：2006-10-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：2000-06-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
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更新日期：1990-08-01 00:00:00
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journal_title：Journal of lipid research
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doi：
更新日期：1986-07-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 临床试验,杂志文章
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1975-07-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1980-09-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.m200075-jlr200
更新日期：2002-07-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1997-09-01 00:00:00
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journal_title：Journal of lipid research
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journal_title：Journal of lipid research
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doi：
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journal_title：Journal of lipid research
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doi：
更新日期：1989-11-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1982-09-01 00:00:00
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pub_type： 杂志文章,随机对照试验
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更新日期：2019-06-01 00:00:00
abstract：:The sequences of the plasma apolipoproteins have a high degree of internal homology as they contain several 22-mer internal repeats. These amphipathic helical repeats are considered as the structural and functional units of this class of proteins. We proposed that the 22-mer repeats of the plasma apolipoproteins consi...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1995-08-01 00:00:00
abstract：:In this article we report the effects of low and high fat diets on the arterial thrombosis tendency in rats. The animal system used was the aorta loop model, in which we compared the effect of saturated (hardened coconut oil, HCO) and unsaturated (sunflower seed oil, SSO; corn oil, CO) fatty acids on the arterial thro...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：2001-07-01 00:00:00
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journal_title：Journal of lipid research
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doi：10.1194/jlr.M050567
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更新日期：2010-08-01 00:00:00
abstract：:Zonation affects liver parenchymal cell function and metabolism as well as nonparenchymal cell activation, but whether VLDL production is zonated has yet to be elucidated. Infection induces enhanced VLDL secretion by the liver. Ex vivo studies were undertaken to examine the liver heterogeneity for VLDL formation and s...
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doi：10.1194/jlr.M500003-JLR200
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