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Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cell surface anionic sites on primary and transformed cultures of human vascular endothelium were studied using cationized ferritin (CF) as an ultrastructural marker. The native distribution of anionic sites on the upper (free) surfaces of cells, fixed in situ with glutaraldehyde, was uniform. Binding of the polycationic ligand, CF, in unfixed cells induced redistribution of anionic sites. Rapid formation of discrete patches of CF particles was followed by reappearance of binding between patches, movement of surface-bound CF into intercellular clefts, and endocytosis, over the next 30 min. Aldehyde-fixed cells, detached from the culture surface, bound CF on both upper and lower surfaces. The distribution and mobility of negatively charged membrane components in vascular endothelium may have relevance for thrombosis, atherogenesis, and vascular permeability.
Atherosclerosis 1979 Jan
PMID:Distribution and movement of anionic cell surface sites in cultured human vascular endothelial cells. 46 14

Low density lipoprotein (LDL) oxidation mediated by phorbol myristate acetate (PMA)- and formylmethionylleucylphenylalanine (FMLP) -stimulated human neutrophils was enhanced by 70% in the presence of ferritin. Iron released from ferritin by the superoxide anion generated in the respiratory burst of stimulated neutrophils is shown to be involved in lipoprotein oxidation. Ascorbate (100 microM), superoxide dismutase (10 micrograms/ml) and uric acid (430 microM) showed inhibitory effects of 30% [corrected], 70% and 50% on LDL oxidation, respectively. Ceruloplasmin (2.7 microM) potentiated LDL oxidation by stimulated neutrophils and ferritin, both alone and in the presence of methionine. Methionine (1 mM) and catalase (30 micrograms/ml) increased LDL oxidation by stimulated neutrophils and ferritin. These data suggest that LDL oxidation by stimulated neutrophils and ferritin may be relevant in inflammation when both neutrophils and ferritin are increased.
Atherosclerosis 1992 Dec
PMID:Low density lipoprotein oxidation by stimulated neutrophils and ferritin. 133 54

Phagocyte-mediated oxidant damage to vascular endothelium is likely involved in various vasculopathies including atherosclerosis and pulmonary leak syndromes such as adult respiratory distress syndrome. We have shown that heme, a hydrophobic iron chelate, is rapidly incorporated into endothelial cells where, after as little as 1 h, it markedly aggravates cytotoxicity engendered by polymorphonuclear leukocyte oxidants or hydrogen peroxide (H2O2). In contrast, however, if cultured endothelial cells are briefly pulsed with heme and then allowed to incubate for a prolonged period (16 h), the cells become highly resistant to oxidant-mediated injury and to the accumulation of endothelial lipid peroxidation products. This protection is associated with the induction within 4 h of mRNAs for both heme oxygenase and ferritin. After 16 h heme oxygenase and ferritin have increased approximately 50-fold and 10-fold, respectively. Differential induction of these proteins determined that ferritin is probably the ultimate cytoprotectant. Ferritin inhibits oxidant-mediated cytolysis in direct relation to its intracellular concentration. Apoferritin, when added to cultured endothelial cells, is taken up in a dose-responsive manner and appears as cytoplasmic granules by immunofluorescence; in a similar dose-responsive manner, added apoferritin protects endothelial cells from oxidant-mediated cytolysis. Conversely, a site-directed mutant of ferritin (heavy chain Glu62----Lys; His65----Gly) which lacks ferroxidase activity and is deficient in iron sequestering capacity, is completely ineffectual as a cytoprotectant. We conclude that endothelium and perhaps other cell types may be protected from oxidant damage through the iron sequestrant, ferritin.
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PMID:Ferritin: a cytoprotective antioxidant strategem of endothelium. 151 45

The effect of hypercholesterolemia on the platelet surface charge was examined in rabbits fed a lipid-rich diet (0.5% cholesterol and 5% butter). The strong anionic sites were detected with cationized ferritin (CF) pI 8.4, and the sialic acid concentration was evaluated by biochemical assays. In normal rabbits (average plasma cholesterol 0.36 +/- 0.05 mg/ml, and total platelet sialic acid 30.03 +/- 6 micrograms/mg protein) the platelet surface displayed a homogeneous distribution of CF, which also labeled the open canalicular system. Beginning with the third week of diet, at a plasma cholesterol level of 4.6 +/- 0.3 mg/ml, a reduction in the overall platelet negative charge was observed. As the diet progressed and the plasma cholesterol level increased, the CF binding to platelet surface diminished up to an almost total disappearance when the plasma cholesterol reached 18 mg/ml (the 20th week of diet). At the same time a progressive decrease in the sialic acid content up to 5.1 micrograms/mg protein was detected. These results suggest that diet-induced hyperlipidemia causes significant alterations in the platelet surface negative charge, especially in the sialic acid content.
Atherosclerosis 1988 Jul
PMID:Changes in the platelet surface charge in rabbits with experimental hypercholesterolemia. 321 61

The adhesion of immunoglobulins (IgG) and beta-migrating very low density lipoproteins (beta-VLDL) to aortic valve cusps from normolipidemic and hypercholesterolemic rabbits is associated with cytochemical changes in the endothelial glycocalyx. Endothelial surface changes are characterized by (1) enzymatic degradations with neuraminidase (NEU), chondroitinase ABC (CABC) or AC, and heparitinase (HPT); and (2) affinity cytochemistry with avidin-ferritin, protein A-HRP, and beta-VLDL-colloidal gold. NEU facilitated IgG deposition on cells from normolipid animals; however, tandem treatment with NEU and CABC increased beta-VLDL but prevented IgG interactions. The addition of HPT was required to eliminate beta-VLDL activity. The cells lining the arterial surfaces of cusps from hypercholesterolemic animals were reactive for endogenous IgG and beta-VLDL-gold. CABC enhanced the binding of the latter but removed most of the IgG. All reactivity was prevented by CABC and HPT. These findings suggest that the reduction of sialic acid residues and exposure of deeper lying glycosaminoglycans in the endothelial glycocalyx favor the interaction of blood-borne elements at natural sites of disturbed blood flow in dietary hypercholesterolemia.
Atherosclerosis 1987 Dec
PMID:Interactions of IgG and beta-VLDL with aortic valve endothelium from hypercholesterolemic rabbits. 332 1

Endothelial uptake of cationized ferritin (CF, pI greater than 9.0) was investigated in the rabbit aorta. After in situ perfusion with CF at concentrations less than 0.35 mg/ml in Tyrode's solution, the endothelial plasmalemmal membrane was partially covered by a ferritin monolayer except at some vesicle necks and regions of cell overlap where particles aggregated. At a concentration of 0.5 mg/ml, CF entered all luminal vesicles and bound to the membrane as a uniform layer usually several particles deep. A steady state was reached after 5 s; particle binding and vesicle filling were not affected by perfusion flow rate up to 20 ml/min. The number of particles per loaded vesicle (F/NL) increased with the density of particles at vesicle necks (PDv), suggesting that particle concentration in the vesicle was in equilibrium with that at the neck. At CF concentrations above 1 mg/ml, binding sites at vesicle necks and elsewhere on the membrane became saturated and luminal vesicles became maximally loaded. Under these conditions, F/NL was greater than that expected for equilibrium with the PDv found. Our findings indicate that anionic sites at vesicle necks and cell overlaps are more strongly negatively charged than elsewhere, and suggest that CF vesicle loading is regulated by the degree of binding at the neck and by the relative strength of the attractive forces at the neck and the vesicle interior.
Atherosclerosis 1985 May
PMID:Regulation of aortic endothelial vesicular uptake of cationized ferritin by plasmalemmal binding. 400 94

The surface sialic acid content of aortic endothelial cells in vitro was substantially lower in sparse cultures than at confluence. Binding of LDL to endothelial cells did not change at different culture densities and was unaffected by brief pretreatment with neuraminidase to partially remove surface sialic acid residues. In contrast, internalization of LDL declined by a factor of 3 between low density cell cultures and confluent monolayers; neuraminidase pretreatment increased LDL uptake and the effect was most marked (greater than 10-fold) at confluence. Pretreatment with cationised ferritin, which removed most of the surface sialic acid residues as well as glycosaminoglycans, increased LDL internalization by up to 20-fold, again with most effect on confluent monolayers. Thus LDL uptake is inversely correlated with sialic acid content. We conclude that changes in the surface density of sialic acid (and possibly other charged) residues significantly modulate endothelial LDL uptake, and suggest that focal increases in LDL accumulation during atherogenesis may be related to alterations in endothelial endocytic properties at sites of increased cell turnover or damage.
Atherosclerosis 1984 Oct
PMID:Surface determinants of low density lipoprotein uptake by endothelial cells. 649 41

The early events in coronary artery atherosclerosis in White Carneau pigeons were studied by combined scanning and transmission electron microscopy. Endothelial cells throughout the right coronary artery were elongate in shape, having an axial ratio (width + length) of 0.48 +/- 0.03, and were oriented with the long axis parallel to the direction of blood flow. Deviation in both orientation and morphology were found in control birds in zones of high probability for disease. Endothelial cells in the high predilection zones were less elongate in shape, having an axial ratio of 0.69 +/- 0.04, and had poorly defined margins and a paucity of microvilli. These less elongate cells were on the average 50 per cent larger (surface area of 147.9 +/- 13.3 versus 93.4 +/- 5.5 sq. microns for the typical cell) than the normal endothelial cell. Upon cholesterol challenge, the percentage of elongate cells decreased in the high propensity zones within the first few weeks, and following 8 weeks of cholesterol challenge the less elongate cells were associated with nascent atherosclerotic lesions. In addition to these large irregularly shaped endothelial cells, the early lesions characteristically were encircled by small cells having prominant nuclei and a large number of microvilli clustered over the nuclear area. Continuation of the cholesterol diet beyond 36 weeks resulted in progressive lesion enlargement and the selective binding of blood cells to the lesion periphery. This margination of blood cells was maximal at 36 weeks when the process was evident in 60 per cent of the cholesterol-fed animals. With further prolongation of cholesterol challenge, adherent cells were found in only 25 per cent of the birds. The surface events observed by scanning electron microscopy were correlated with ultrastructural changes in the endothelial glycocalyx. Cholesterol challenge resulted in a significant reduction in both the amount of ruthenium red stain and the number of cationized ferritin particles which were bound to luminal surfaces. In control diet animals, the glycocalyx thickness was in the range of 700 to 1000 A, with the thinnest areas being those in zones of high disease predilection and numerous nonelongate endothelial cells. When analyzed on an individual cell basis, the villus portions of the endothelial surface (glycocalyx thickness, 436 A) averaged 64 per cent thinner than the nonvillus portions of the cell. Upon cholesterol challenge, the glycocalyx was reduced in all arterial zones to 450 A, which approximated the thickness found for microvilli. Our results clearly document changes in endothelial morphology during the early stages of coronary atherosclerosis. These morphologic features are discussed with respect to the role the altered cells may play in disease progression.
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PMID:Endothelial surface characteristics in pigeon coronary artery atherosclerosis. I. Cellular alterations during the initial stages of dietary cholesterol challenge. 706 18

Iron, a major oxidant in vivo, could be involved in atherosclerosis through the induction of the formation of oxidized LDL, a major atherogenic factor. This study was designed to test this hypothesis experimentally. Four groups of New Zealand White rabbits were included: iron-overloaded/hypercholesterolemic (group A, n = 8), iron-overloaded (group B, n = 6), hypercholesterolemic (group C, n = 6), and untreated (group D, n = 6). Iron overload was achieved by the intramuscular administration of 1.5 g of iron dextran divided in 30 doses. Hypercholesterolemia was produced by feeding rabbit chow enriched with 0.5% (wt/wt) cholesterol. Serum iron, ferritin, cholesterol, triglycerides, and lipoperoxides in serum were measured throughout the study. Lipoperoxides were measured at the end of the study in liver, aorta, and spleen homogenates. Aortas of groups A and C had multiple lesions; however, group A had greater lesional involvement than group C (P < .05). Lesions were not observed in rabbits fed normal chow (group D). As expected, serum iron and ferritin were above normal levels in groups A and B. Serum cholesterol increased in groups A and C. Lipoperoxides in liver and spleen homogenates of iron-overloaded rabbits were increased. Interestingly, iron deposits were seen by ultrastructural studies in the arterial walls of rabbits in groups A and B. Our study suggests that iron overload augments the formation of atherosclerotic lesions in hypercholesterolemic rabbits.
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PMID:Iron overload augments the development of atherosclerotic lesions in rabbits. 754 98

Low density lipoprotein (LDL), if it becomes oxidized, develops several unique properties including the capacity to provoke endothelial cytotoxicity via metal-catalyzed free radical-mediated mechanisms. As were previously have shown that iron-catalyzed oxidant injury to endothelial cells can be attenuated by the addition of exogenous iron chelators such as the lazaroids and deferoxamine, we have examined whether the endogenous iron chelator, ferritin, might provide protection from oxidized LDL. LDL oxidized by iron-containing hemin and H2O2 is toxic to endothelial cells in a time- and dose-dependent fashion. Endothelial cell ferritin content is increased by pretreatment of cells with iron compounds or by the direct addition of exogenous apoferritin; ferritin-loaded cells are markedly resistant to the toxicity caused by oxidized LDL. Iron inactivation by ferritin depends on its ferroxidase activity. When a recombinant human ferritin heavy chain mutant, 222, which is devoid of ferroxidase activity, is added to endothelial cells, unlike the excellent protection afforded by the wild-type recombinant heavy chain, endothelial cells are not protected from oxidized LDL. To assess the in vivo relevance of our observation, we examined human coronary arteries of cardiac explants taken from patients with end-stage atherosclerosis. Large amounts of immunoreactive ferritin are focally detected in atherosclerotic lesions, specifically in the myofibroblasts, macrophages, and endothelium without a notable increase in Prussian blue-detectable iron. These findings suggest that ferritin may modulate vascular cell injury in vivo.
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PMID:Ferritin protects endothelial cells from oxidized low density lipoprotein in vitro. 767 89


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