Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There is now considerable evidence that peroxisomes not only have a role in cholesterol oxidation but also in cholesterol biosynthesis. Specifically, peroxisomes contain at least two enzymes necessary for the initial steps in cholesterol synthesis, i.e., thiolase and mevalonate kinase. The rate-limiting enzyme in cholesterol synthesis, 3-hydroxy-3-methylglutaryl coenzyme A reductase, is also localized in peroxisomes and exhibits a cyclic variation distinct from that of the reductase found in the endoplasmic reticulum. The largest concentration of cellular sterol carrier protein-2 is localized in peroxisomes as well as a number of enzymes required for the conversion of lanosterol to cholesterol. Furthermore, peroxisomes are involved in the in vitro synthesis of cholesterol and dolichol from mevalonate and have been shown to contain significant levels of apolipoprotein E, a major constituent of several classes of plasma lipoproteins. Moreover, cholesterol synthetic capacity is impaired in cultured skin fibroblasts obtained from patients with peroxisomal deficiency diseases.
Am J Respir Cell Mol Biol 1992 Oct
PMID:The role of peroxisomes in cholesterol metabolism. 135 76

Entorhinal cortex lesions (ECL) that damage the perforant path to the hippocampus induce rapid increases of apolipoprotein E (apo E) mRNA in the hippocampus. Apo E mRNA was localized in astrocytes by in situ hybridization in combination with immunocytochemistry for glial fibrillary acidic protein (GFAP). Unilateral ECL also increased hippocampal GFAP mRNA, with increases preceding those of apo E mRNA. The apo E mRNA and GFAP mRNA responses were transiently bilateral in non-denervated zones. The timing of response in apo E mRNA to deafferentation supports suggestions that apo E has roles in membrane remodelling during responses to neuron injury.
Brain Res Mol Brain Res 1991 Sep
PMID:Astrocytic apolipoprotein E mRNA and GFAP mRNA in hippocampus after entorhinal cortex lesioning. 166 18

Evidence is given for altered gene expression in the hippocampus in response to entorhinal cortex lesioning. Three RNA markers encoding glial fibrillary acidic protein, apolipoprotein E and alpha-tubulin were isolated from a rat hippocampal cDNA library by differential screening with cDNA probes from entorhinal cortex lesioned and control rat hippocampus RNA. By Northern blot analysis, mRNA for apolipoprotein E and alpha-tubulin increased to peak around 6 days after the lesion and returned to near control level at 30 days. The increased synthesis of both mRNAs coincides with the acute phase of synaptogenesis, protein synthesis, and polyribosomes accumulation in the deafferented hippocampal area.
Brain Res Mol Brain Res 1991 Feb
PMID:Cloning of hippocampal poly(A) RNA sequences that increase after entorhinal cortex lesion in adult rat. 167 53

The presence of specific receptors for apolipoprotein B (low-density lipoproteins) and apolipoprotein E (HDL-E) on Hep-G2 cells and human skin fibroblasts was studied by chemical methods and by electron microscopy using a differential gold labeling technique. Fibroblasts bound both types of lipoproteins to one and the same receptor (B/E receptor) as deduced from competition experiments with HDL-E and LDL. Labeled HDL-E, on the other hand, was only partially displaced by cold LDL but was completely displaced by unlabeled HDL-E. Scatchard analysis of lipoprotein binding to Hep-G2 cells revealed an approx 10 times higher binding affinity of apoE-containing lipoproteins as compared to apoB-containing ones. No differences between apoE- or apoB-containing lipoproteins with respect to the morphology of cell binding and intracellular processing were observed. The results are compatible with the concept that Hep-G2 cells possess two kinds of receptors, one specific for apoB- and apoE-containing lipoproteins (B/E receptor) and another specific for apoE only. From these studies we conclude that Hep-G2 cells may serve as a suitable model for studying the lipoprotein metabolism in the liver.
Exp Mol Pathol 1987 Jun
PMID:The existence of B/E and E receptors on Hep-G2 cells: a study using colloidal gold- and 125I-labeled lipoproteins. 303 69

Human apolipoprotein E is a component of several classes of circulating plasma lipoproteins. In addition to binding lipids, this apolipoprotein, which is composed of two structural domains, mediates some lipoprotein-receptor interactions by binding to the low density lipoprotein receptor. The receptor-binding function, as well as some lipid-binding capability, is contained in the amino-terminal structural domain of apolipoprotein E. Thrombin-catalyzed hydrolysis of apolipoprotein E yields a fragment (residues 1 to 191) that has the same properties as, and seems to be a good model for, the amino-terminal domain. Crystals of this amino-terminal fragment suitable for high-resolution X-ray diffraction experiments have now been grown. The crystals belong to the orthorhombic space group P2(1)2(1)2(1) and have unit cell dimensions of a = 86.0 A, b = 40.9 A, and c = 53.3 A (1 A = 0.1 nm). This is the first human serum apolipoprotein to be crystallized.
J Mol Biol 1988 Jul 05
PMID:Crystallization and preliminary X-ray diffraction studies on the amino-terminal (receptor-binding) domain of human apolipoprotein E3 from serum very low density lipoproteins. 317 12

The effect of apolipoprotein E (apo E) common genotypes on fasting retinyl palmitate (RP) level was studied in 344 white individuals, of which 130 had intimal thickening of the carotid artery ("cases") and 214 were controls. In this sample the common apo E genotypes possessed a statistically significant effect on fasting RP level in cases, while in controls the effect observed was not statistically significant. It is suggested that the effect of apo E may be expressed at the level of remnant clearance particles. Additionally, in cases other traits interact with the apo E genotype to influence fasting RP level.
Biochem Mol Med 1995 Aug
PMID:Effect of apolipoprotein E polymorphism on fasting retinyl palmitate level. 758 73

We have investigated the effect of genotypes of apolipoprotein E (ApoE) on the pathologies found in Alzheimer's disease (AD) and its related gene expression in 38 aged human brains obtained from consecutive autopsied cases. ApoE2/3, -3/3, -3/4, and -4/4 were typed in those aged brains, with ApoE3/3 being most prevalent. The AD pathologies were undetectable in ApoE2/3 brains, but were frequently observed in the other ApoE groups. In ApoE3/3 brains, 55%, 34%, and 24% of the cortical sections examined showed senile plaques (SPs), neurofibrillary tangles (NFTs), and cerebral amyloid angiopathy (CAA), respectively. In ApoE4/4 brains, the SP formation was significantly higher. The ApoE genotype neither affected ApoE, APP, or tau mRNA level, nor the differential expression of the latter two. These results suggest that ApoE4/4 accelerates and ApoE2/3 decelerates the development of the AD pathologies in the aged brain, but this is not through alterations of the APP and tau gene expression.
Brain Res Mol Brain Res 1995 Mar
PMID:Apolipoprotein E genotype, Alzheimer's pathologies and related gene expression in the aged population. 777 5

Extrahepatic tissues including the adrenal cortex are capable of synthesizing apolipoprotein E (apoE). Locally synthesized apoE is believed to affect cellular uptake, transport and redistribution of cholesterol within that organ. We and another laboratory have previously reported that the adrenal cortex of aged rats has an elevated cholesteryl ester content. The aim of this work was to investigate whether this elevation is accompanied by increased adrenal apoE levels in aged rats. A Western blotting technique with polyclonal goat anti-human-apoE antiserum was employed as a probe for studies. The results showed that: (a) anti-human-apoE antiserum not only detected apoE in human plasma and adrenal homogenate, but also cross-reacted with a protein (or proteins) resembling apoE in rat plasma and adrenal homogenate (or supernatant) with a molecular weight of 34,000-36,000; (b) rat adrenal apoE concentration (per unit weight of protein) increased with age; (c) the increase did not result from blood trapped in the gland, because after organ perfusion the adrenal of aged rats persistently exhibited 58% more apoE than that of young animals. In conclusion, rat adrenal apoE concentration appears to increase with age. Whether this increase mechanistically causes the accumulation of cholesteryl esters in the aged rat adrenal remains to be investigated.
Mol Cell Endocrinol 1995 Jan
PMID:Aging in rats is associated with an increase in adrenal apolipoprotein E. 779 39

An association between the 19q13.2 chromosomal region and Alzheimer's disease (AD) has been reported in AD families and for sporadic AD. Recent observations provide evidence that the epsilon 4 allele of the apolipoprotein E gene (APOE), located in this region, is a risk factor for late-onset AD. Within this region, other genes possibly involved in the pathophysiology of AD and in strong linkage disequilibrium with the APOE locus may be responsible for this association. To test this hypothesis, we analysed the allelic distribution of four polymorphic genetic markers flanking the APOE gene (D19S178 (CA)n repeat, D19S47 (CA)n repeat, APOCI HpaI restriction fragment length polymorphism, APOCII (CA)n repeat). We performed these analyses in a sample of late-onset sporadic cases (n = 36) versus controls (n = 38), and in a sample of early-onset sporadic cases (n = 34) versus controls (n = 36). Early-onset cases were analysed for two cut-offs with late-onset: less than 60 and less than 65. We observed a significant increased frequency of the APOE epsilon 4 allele in late-onset and early-onset AD with ages at onset less than 60 and less than 65. The adjusted odds ratio (OR) of the bearers of at least one APOE epsilon 4 allele was 4.10 ([1.84;9.16]) when estimated in both populations with a logistic regression model. Surprisingly, the odds ratio of the bearers of at least one APOE epsilon 2 allele was also significant and equal to 0.11 ([0.02;0.50]) suggesting a possible protective effect.(ABSTRACT TRUNCATED AT 250 WORDS)
Hum Mol Genet 1994 Apr
PMID:Apolipoprotein E, epsilon 4 allele as a major risk factor for sporadic early and late-onset forms of Alzheimer's disease: analysis of the 19q13.2 chromosomal region. 806

We report the cloning of a 3656-bp cDNA encoding a putative human very low density lipoprotein (VLDL)/apolipoprotein E (ApoE) receptor. The gene encoding this protein was mapped to chromosome 9pter-p23. Northern analysis of human RNA identified cognate mRNAs of 6.0 and 3.8 kb with most abundant expression in heart and skeletal muscle, followed by kidney, placenta, pancreas, and brain. The pattern of expression generally paralleled that of lipoprotein lipase mRNA but differed from that of the low density lipoprotein (LDL) receptor and the low density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor (LRP), which are members of the same gene family. VLDL/ApoE receptor message was not detected in liver, whereas mRNAs for both LDL receptor and LRP were found in hepatic tissue. In mouse 3T3-L1 cells, VLDL/ApoE receptor mRNA was induced during the transformation of the cells into adipocytes. Expression was also detected in human choriocarcinoma cells, suggesting that at least part of the expression observed in placenta may be in trophoblasts, cells which would be exposed to maternal blood. Expression in brain may be related to high levels of ApoE expression in that organ, an observation of potential relevance to the recently hypothesized role for ApoE in late onset Alzheimer disease. Our results suggest that the putative VLDL/ApoE receptor could play a role in the uptake of triglyceride-rich lipoprotein particles by specific organs including striated and cardiac muscle and adipose tissue and in the transport of maternal lipids across the placenta. The findings presented here, together with recent observations from other laboratories, bring up the possibility that a single gene, the VLDL/ApoE receptor, may play a role in the pathogenesis of certain forms of atherosclerosis, Alzheimer disease, and obesity.
Somat Cell Mol Genet 1993 Nov
PMID:Cloning of a cDNA encoding a putative human very low density lipoprotein/apolipoprotein E receptor and assignment of the gene to chromosome 9pter-p23. 812 15


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