Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sprague-Dawley rats injected i.v. with a single dose of puromycin aminonucleoside (PAN) developed massive proteinuria five days later. Electron microscopic studies of perfusion-fixed glomeruli showed that loss of epithelial foot processes and their replacement by flattened expanses of epithelial cytoplasm began at two days and was extensive by four days after the injection of PAN. At and after five days (correlating with the onset and persistence of massive proteinuria), areas of focal loss of the epithelial covering on the outside of the glomerular basement membrane (GBM) were observed in 30% of glomeruli. Intravenously administered ferritin was distributed normally in most sections of the GBM of nephrotic animals, but abnormally deep penetration of particles was observed in GBM segments that lacked an external covering of epithelium. The same changes were found following in situ fixation of superficially placed glomeruli of Munich-Wistar rats with PAN nephrosis. We propose that the massive, early proteinuria in PAN nephrosis may be primarily due to a glomerular epithelial lesion, leading to scattered focal defects in the external covering of the GBM. Increased bulk flow of glomerular filtrate across the GBM in such areas may explain the highly selective proteinuria found in this form of the nephrotic syndrome.
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PMID:An ultrastructural study of the mechanisms of proteinuria in aminonucleoside nephrosis. 110 66

Sprague-Dawley rats, 6 with aminonucleoside nephrosis and 6 controls, were intravenously injected with human liver ferritin isolated from post mortem liver, and their 24-h urine samples were examined for human ferritin by immunoradiometric assay. In rats with aminonucleoside nephrosis, the amount of excreted ferritin in urine was forty times greater than in control rats. Much more monomeric ferritin was excreted than that of polymeric ferritin. We are the first to have utilized human liver ferritin as a tracer to measure a minor amount of ferritin by a commercially available kit. Our present study seems to indicate a critical role for glomerular basement membrane as a size barrier.
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PMID:Human liver ferritin as a new tracer for studying glomerular permeability. 262 44

Quantitative electron microscopic autoradiography was employed to determine the changes in the binding of 125I-cationic ferritin (CFI, pI approximately 7.2 to 7.4) to the anionic sites of the glomerular basement membrane (GBM) of rats following the induction of nephrosis. Animals were rendered nephrotic by a single intravenous injection of puromycin aminonucleoside (PAN) and sacrificed 0, 7, 14, and 21 days after its administration. CFI (10 mg/mCi/100 g body weight) was given intravenously. The kidneys were subsequently fixed by perfusion and processed for electron microscopic autoradiography. The mean grain densities over the GBMs on 0, 7, 14, and 21 days of PAN nephrosis were 1.50 +/- 0.04, 1.49 +/- 0.05, 1.50 +/- 0.05, and 1.51 +/- 0.04, respectively. These results indicate that there are no significant alterations in the anionic sites rich in heparan sulfate proteoglycan during the entire course of PAN nephrosis.
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PMID:Unaltered anionic sites of glomerular basement membrane in aminonucleoside nephrosis. 648 65

Changes in the permeability of the glomerular capillary wall (GCW) to native ferritin (NF), following detachment of the visceral epithelium from the glomerular basement membrane (GBM) were investigated. Detachment was induced by either perfusing kidneys with highly purified neuraminidase or by the induction of nephrosis through administration of puromycin aminonucleoside (PAN). Both experimental treatments resulted in marked glomerular ultrastructural changes which were characterized by focal detachment of the visceral epithelium from the GBM, replacement of the normal pattern of interdigitating foot processes with flattened expanses of continuous epithelium at certain areas of the GCW, and a generalized loss of sialic acid-rich epithelial cell cost in areas where the epithelium was detached as well as where it remained adherent. These changes were more frequent and prominent in the paramesangial regions of the glomeruli. When experimentally treated kidneys were perfused with NF, the tracer leaked into the urinary spaces in those areas of the GBM where the epithelium was detached. By contrast, in those areas of the GCW where the epithelium remained adherent, the tracer localized within the GBM mainly at the level of the lamina rara interna (LRI), and none of it appeared in the urinary spaces. Nephrotic and neuraminidase control kidneys were ultrastructurally normal, NF localizing mainly in the inner layers of the GBM. These data are consistent with the idea that the firm attachment of the epithelial foot processes to the GBM plays a vital role in determining the permselectivity properties of the GCW to plasma macromolecules.
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PMID:Altered glomerular permeability as a result of focal detachment of the visceral epithelium. 709 74

Alterations in the permeability of the glomerular basement membrane (GBM) towards native ferritin (NF) and iodinated albumin (125I-BSA) following removal of the major glycosaminoglycans (GAGs) of the GBM, heparan sulfate (HS) and hyaluronic acid (HA), were assessed utilizing the techniques of routine electron microscopy and autoradiography, respectively. Kidneys were incubated with heparinase (to degrade the GAGs of the GBM) and subsequently perfused with either NF or 125I-BSA. Control kidneys, which were not treated with heparinase, showed a low permeability to both tracers, with NF being confined to the lamina rara interna and 125I-BSA exhibiting a low level of passage into the urinary spaces (as indicated by a low density of autoradiographic grains over the urinary spaces). After heparinase treatment there was an increase in the permeability of the GBM such that both NF and 125I-BSA passed through the GBM in larger quantities and entered the urinary spaces. Perfusion of cationized ferritin (CF) into control kidneys revealed this probe to bind to the HS-rich anionic sites present within the GBM. Treatment with heparinase resulted in an abolition of the CF binding thereby indicating that the sites are composed mainly of HS and that HS plays a key role in establishing the permeability properties of the GBM. The changes in the pattern of distribution and density of the anionic sites of the GBM following induction of nephrosis was also studied. Animals were rendered nephrotic by subcutaneous injections of an aminonucleoside of puromycin and their kidneys subsequently perfused with either CF or cationized cytochrome c. No difference in either the pattern of distribution on density of the anionic sites in the GBM of nephrotic kidneys was observed when compared to nonnephrotic controls; thus indicating that the proteinuria associated with aminonucleoside nephrosis might be due to changes in components of the glomerular capillary wall other than the anionic sites.
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PMID:Glycosaminoglycans of the glomerular basement membrane in normal and nephrotic states. 730 62

The aminonucleoside of puromycin induces proteinuria and renal damage when given to rats. Aminonucleoside of puromycin was administered to male Wistar-Furth rats as a single intravenous injection in a dose of 15 mg. per 100 gm. of body weight. The animals were studied 9 days later when the mean urinary protein was 175 mg. per 24 hours. Evidence of glomerular epithelial cell injury included massive obliteration of foot processes, appearance of microvilli, protein reabsorption droplets, extreme attenuation of cytoplasm with formation of blebs, and focal detachment of epithelial cells from glomerular basement membrane. An increase in both the amount of mesangial matrix and the number of mesangial cells was also observed. The fractional clearance (C/GFR) of anionic horseradish peroxidase had increased 18.5 times as compared to control values and was nearly equal to the C/GFR of neutral horseradish peroxidase in the experimental rats. The C/GFR of cationic horseradish peroxidase was decreased by one-third so that it approximated the C/GFRs of both anionic and neutral horseradish peroxidase. These findings indicate a nearly complete loss of the charge-selective barrier to filtration. In addition, C/GFRs of tritiated uncharged dextrans with a range of molecular radii from 18 to 58 Angstrom (A) were determined. The C/GFRs of dextrans (alpha e less than 30 A) were decreased in the experimental rats as compared to C/GFRs of dextrans of corresponding molecular size in control rats. However, the C/GFRs of dextrans (alpha e greater than 38A) were increased in experimental as compared to control rats. Further, both anionic and cationic ferritin (alpha e = 61 A) were observed in the urinary space near denuded areas of glomerular basement membrane. These results indicate that the size-selective properties of the glomerular barrier to filtration have been modified with decreased C/GFR of small molecules and increased C/GFR of large molecules. Thus, the proteinuria of aminonucleoside nephrosis in rats occurs secondary to alterations in both the charge- and size-selective barriers to glomerular filtration.
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PMID:Alterations in the charge and size selectivity barrier of the glomerular filter in aminonucleoside nephrosis in rats. 746 51

To clarify the roles of the glomerular basement membrane (GBM) in filtration mechanisms, human liver ferritin was used for the first time as a tracer. Urinary excretion of human liver ferritin was measured and the injected ferritin was tracked under electron microscopy. Puromycin aminonucleoside (PAN) nephrosis was induced in Sprague Dawley rats and normal saline was injected into control rats. Monomeric and polymeric human ferritin were isolated from post mortem samples. Both kinds of human liver ferritin were injected into the experimental and control rats and urine samples were examined for human ferritin by radioimmunoassay. Rats with PAN nephrosis excreted approximately 33 times more monomeric ferritin than the controls. Appreciably more monomeric ferritin was excreted than polymeric ferritin. In control rats, monomeric ferritin particles were restricted in the lamina rara interna and inner aspect of the glomerular basement membrane 30 min after injection. On the other hand, in rats with PAN nephrosis, monomeric ferritin particles were seen throughout the width of the GBM and in the epithelial cells. With human liver ferritin, we were able to demonstrate the escape of the ferritin into the urine in addition to conducting the conventional electron microscopic tracer study of the glomerular capillary wall. Human liver ferritin shows potential as a useful tracer in the study of glomerular permselectivity.
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PMID:Studies on the glomerular permeability with human liver ferritin. 813 33

Ferritin was used as a tracer to study the mechanism by which proteins are segregated into droplets by the visceral epithelium of glomerular capillaries. In glomeruli from both normal and aminonucleoside-nephrotic rats ferritin molecules introduced into the general circulation penetrated the endothelial openings and were seen at various levels in the basement membrane. Striking differences between nephrotic and controls were seen only in the amount of ferritin incorporated into the epithelium. In normal animals, a few ferritin molecules were seen in small invaginations of the cell membrane limiting the foot processes, within minute vesicles in the epithelium, or within occasional large vacuoles and dense bodies. In nephrotics, epithelial pinocytosis was marked, and numerous ferritin molecules were seen within membrane invaginations and in small cytoplasmic vesicles at all time points. After longer intervals, the concentration of ferritin increased in vacuoles and particularly within the dense bodies or within structures with a morphology intermediate between that of vacuoles and dense bodies. In nephrotic animals cleft-like cavities or sinuses were frequently encountered along the epithelial cell surface facing the urinary spaces. Some of these sinuses contained material resembling that filling the dense bodies except that it appeared less compact. The findings suggest that ferritin molecules-and presumably other proteins which penetrate the basement membrane-are picked up by the epithelium in pinocytotic vesicles and transported via the small vesicles to larger vacuoles which are subsequently transformed into dense bodies by progressive condensation. The content of the dense bodies may then undergo partial digestion and be extruded into the urinary spaces where it disperses. The activity of the glomerular epithelium in the incorporation and segregation of protein is similar in normal and nephrotic animals, except that the rate is considerably higher in nephrosis where the permeability of the glomerular basement membrane is greatly increased.
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PMID:Segregation of ferritin in glomerular protein absorption droplets. 1382 9

Ferritin was used as a tracer to investigate glomerular permeability in the nephrotic rat. The results were compared with those previously obtained in normal animals. A nephrotic syndrome was induced by 9 daily injections of the aminonucleoside of puromycin. Ferritin was administered intravenously on the 10th day, and kidney tissue was fixed at intervals of 5 minutes to 44 hours after injection of the tracer and examined by electron microscopy. The observations confirmed that at this stage of the experimental nephrotic syndrome the changes affect predominantly the visceral epithelium (loss of foot processes, reduction and modification of urinary slits, and intracellular accumulation of vacuoles and protein absorption droplets). Less extensive changes were found in other layers (reduction of endothelial fenestrae, an increase in the population of "deep" cells, and a thinning and "loosening" of the basement membrane.) At short intervals (5 to 15 minutes) after ferritin administration, the tracer was found at high concentration in the lumen and endothelial fenestrae, and at decreasing concentrations embedded throughout the basement membrane and incorporated into the epithelium (within cytoplasmic vesicles and within invaginations of the plasmalemma facing the basement membrane). After longer intervals (1 to 3 hours) the distribution of the tracer within the capillary wall was similar except that its concentration in the epithelium was higher, and, in addition to plasma membrane invaginations and small vesicles, ferritin also marked larger vacuoles, dense bodies, and intermediate forms. Large accumulations of tracer typically occurred in the spongy areas of the basement membrane, especially in the axial regions. Ferritin also appeared in the endothelium within membrane-limited vacuoles and dense bodies, particularly in the deep cells. After 6 to 44 hours the tracer still occurred in the lumen and throughout the basement membrane. The ferritin deposits in the spongy areas as well as the ferritin-containing vacuoles of the deep endothelium were larger and more numerous. In the epithelium ferritin was found not only within various membrane-limited bodies, but also "free" within the cytoplasmic matrix. These observations indicate that in the nephrotic glomerulus, as in the normal, the basement membrane functions as the main filtration barrier; however, in nephrosis, the basement membrane is defective and allows leakage of increased quantitites of ferritin and presumably plasma proteins. The basement membrane defect appears to be fine and widespread, occurring at or near the molecular level of organization of the filter. The accumulation of unfiltered ferritin in axial regions together with the demonstration of its subsequent phagocytosis by the "deep" endothelial cells suggest that the latter may function in the removal of filtration residues. Finally, the findings indicate that in the nephrotic, as in the normal animal, the epithelium acts as a monitor that recovers, at least in part, the protein which leaks through the filter, and that in nephrosis, the recovering activities of the epithelium are greatly enhanced because of the increased permeability of the basement membrane.
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PMID:Glomerular permeability. II. Ferritin transfer across the glomerular capillary wall in nephrotic rats. 1389 78