Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Livers from normal and nephrotic rats were perfused by the nonrecirculating technique. Nephrosis was studied on the 7th d after the injection of puromycin animonucleoside. Amino acid-labeled lipoproteins (d < 1.21) were isolated from the perfusion medium by agarose column chromatography or by sequential density ultracentrifugation. In both groups of animals, in addition to very low density lipoproteins and nascent high density lipoproteins, column chromatography revealed the presence of a peak of 2-3 x 10(6) daltons. This peak contained lipoproteins of densities corresponding to <1.006, 1.006 < d < 1.02, and 1.02 < d < 1.06, which indicated that rat liver secretes a heterogeneous mixture of triglyceride-rich lipoproteins. The amount of these lipoprotein density classes was measured and their lipid and apoprotein composition and their apoprotein specific activity were determined. In both groups of rats there was a progressive rise in phospholipid and decrease in triglyceride content as the isolation density increased from 1.006 and 1.06. The lipoproteins from the nephrotics had higher amounts of cholesterol. The livers from the nephrotic rats secreted two to three times as much lipoprotein as controls in all density classes in the first 20 min, but during the next 40 min only the 1.02 < d < 1.06 and nascent high density lipoproteins remained at this high level compared to controls. A larger total liver pool of apolipoproteins in nephrotic livers was inferred from their lower specific activities during the first 20 min. The apoprotein composition of liver perfusate lipoproteins from nephrotics differed from controls. There was a 40% decrease in the amount of low molecular weight apoproteins in all density classes, with corresponding increases in apo B and apo E in the triglyceride-rich fractions. The apo A-1 content of nascent HDL was increased from 16% in controls to 52% in nephrotics, with corresponding decreases in apo C and apo E. When these results were combined with specific activity measurements of the individual apoproteins and the net secretion rate of total protein in each lipoprotein class, it was possible to estimate the total amount of each apoprotein secreted and the total incorporation of labeled amino acids into each. The incorporation of label gave results similar to those obtained by direct measurement of the amounts of apoproteins. Apo E secretion was increased by a factor of 1.8, apo B by 2.8, and apo A-1 by 8.4, whereas the secretion of apo C was not significantly altered. We explain these results by postulating that the primary stimulus to hepatic plasma protein synthesis in response to proteinuria is general and that subsequent negative feedback regulation affects individual apolipoprotein synthesis rates. A corollary of this hypothesis is that the biosynthesis and secretion of an apoprotein may be regulated independently of the lipoprotein density class in which it is found.
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PMID:Hepatic secretion of lipoproteins in the rat and the effect of experimental nephrosis. 22 28

Extracorporeal shock wave lithotripsy (ESWL) causes proteinuria. In our study we investigated the protein fractions and the electrolyte composition of the urine in patients who had been treated with ESWL. The aim was to obtain information on the degree and the localisation of the glomerular, tubular or vascular destruction caused by ESWL in humans. A total of 34 patients with stones had been treated with ESWL. As parameters we used: urine output, creatinine clearance, total protein, albumin, immunoglobulin G, N-acetyl-beta-D-glucosaminidase (beta-NAG), alpha-1-microglobulin, the fractional excretion of Na+ and apolipoprotein-A-1. After ESWL treatment proteinuria and albuminuria are found. Our parameters show no deterioration of the glomerula or the tubulus. The increase in apolipoprotein-A-1, a postglomerular parameter, however, is interpreted as a manifestation of vascular destruction after ESWL; this is normally temporary, leaving no permanent damage.
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PMID:[Localization and extent of tissue damage caused by extracorporeal lithotripsy (ESWL)]. 171 30

Our previous paper showed that the glycoprotein of Mr 108,000 (gp108) is one of the major components of rat renal tubular brush border antigens and that an injection of anti-gp108 antiserum in rats induces passive Heymann nephritis with acute and severe proteinuria. In this study, gp108 was identified as a monomer of dipeptidyl peptidase IV (DPP IV). The anti-gp108 antibody was shown to immunoprecipitate DPP IV from Triton-extract of renal tubular membrane fractions. DPP IV was co-purified with gp108 from the Triton-extract by columns of DEAE-cellulose and Bio-gel A-1.5 m. The ratio of DPP IV activity and gp108 content was nearly constant throughout the purification steps. The final purified gp108 showed a high specific activity of DPP IV, comparable to that reported for purified rat DPP IV. These results indicate that gp108 is a monomer of DPP IV.
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PMID:Identification of gp108, a pathogenic antigen of passive Heymann nephritis, as dipeptidyl peptidase IV. 289 1

Passive Heymann nephritis with acute and severe proteinuria was produced in rats by a single injection of heterologous antibody against a purified glycoprotein which consisted of homologous subunits with a molecular weight of 108,000 (gp108). Gp108 was identified as one of the major antigens in rat renal tubular fraction (FX1A) on immunoblotting assay by using total proteins of FX1A and rabbit antiserum against FX1A. A band of gp330, which was identified as a pathogenic antigen of Heymann nephritis by Kerjaschki D and Farquhar MG (Proc Natl Acad Sci USA 79:5557, 1982) was detected as another band by Coomassie blue staining and immunoblotting. Autoantibodies in the sera of FX1A-injected (active Heymann nephritis) rats reacted to the band of gp330 but not to gp108. These results indicate that gp108 is a different glycoprotein from both gp330 and its degradation products. GP108 was subsequently purified to near homogeneity by extraction with Triton X-100, and then DEAE-cellulose and Bio-Gel A-1.5m column chromatographies. On gel permeation chromatography, the purified antigen showed a molecular weight of 310,000, suggesting that it consists of dimer or trimer of gp108. Rabbits immunized with gp108 produced an antibody which showed monospecific binding to gp108. The antibody stained with brush border of proximal renal tubules in addition to the capillary loops in rat glomeruli by indirect immunofluorescence. Injection of rabbit antiserum against gp108 in rats induced severe proteinuria within 2 days. On the 2nd day after the injection, the glomeruli of the animals showed granular immune deposits along the capillary loops in addition to dominant staining of the brush border of the proximal tubules by immunofluorescence. These results indicate that gp108 is a pathogenic antigen in passive Heymann nephritis and that an antibody against gp108 has a nephritogenic and proteinuria-inducing activity.
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PMID:Passive Heymann nephritis with acute and severe proteinuria induced by heterologous antibody against renal tubular brush border glycoprotein gp108. 375 92

We have investigated the possibility that the mild proteinuria in a patient with Tangier disease is directly related to the plasma HDL-deficiency through excretion of apolipoprotein A-I (Mr 28,300). An increased urinary excretion of a 29,000 polypeptide was observed in this patient. However, western blot analysis of the urine showed that this protein was not apolipoprotein A-1 or its precursor form. Subsequent investigations identified the urinary protein as immunoglobulin light chains. The elevated excretion may be a consequence of the patient's plasma polyclonal gammopathy which had resulted from a chronic infection.
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PMID:Urinary proteins in a patient with Tangier disease. 392 43

In experimental nephrosis, a decrease in plasma albumin resulting from proteinuria causes a decreased in the plasma oncotic pressure. The existence of an osmoreceptor, which responds to the low oncotic pressure and produces a factor(s) that signals the liver to increase the secretion of plasma proteins, is postulated. The hyperlipidemia characteristic of the nephrotic syndrome results primarily from increased hepatic secretion of apolipoproteins and lipoproteins representing the entire density spectrum from VLDL, IDL, and LDL to HDL. Not all plasma proteins and apolipoproteins are affected to the same extent. Increased mRNA levels due to increased transcription have been shown for albumin and apolipoprotein A-1 (apoA-1). The increased secretion of VLDL, the major vehicle for triglyceride transport from the liver, appears to be due mainly to posttranscriptional events possibly related to increased lipogenesis. Once proteinuria begins, the demand for amino acids for albumin and apolipoprotein synthesis by the liver is increased. To meet this demand, protein catabolism in the peripheral tissues is increased. One manifestation of this process is a decrease in lipoprotein lipase which reduces VLDL catabolism, contributing to the sustained elevation of plasma VLDL. The spectacular overproduction of apoA-1 in nephrosis in the rat is accompanied by a decreased fractional catabolic rate (FCR), contributing to the maintenance of high levels of HDL. Urinary loss of HDL and its renal catabolism does not account for the decreased FCR. The reason for the decreased FCR is not known. Work with nephrotic rats overexpressing transgenic human apoA-1 has shown that human A-1 forms smaller HDL3-sized particles, rather than the larger HDL2 of the rat. This may contribute to the failure of HDL levels to increase in the human nephrotic syndrome. High plasma VLDL and LDL with normal or low HDL probably account for the increased incidence of coronary artery disease in the nephrotic syndrome.
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PMID:Lipoprotein metabolism in experimental nephrosis. 893 62

The proper functioning of the Cl(-) channel, ClC-5, is essential for the uptake of low molecular mass proteins through receptor-mediated endocytosis in the proximal tubule. Dent's disease patients with mutant ClC-5 channels and ClC-5 knockout (KO) mice both have low molecular mass proteinuria. To further understand the function of ClC-5, endocytosis was studied in LLC-PK(1) cells and primary cultures of proximal tubule cells from wild-type (WT) and ClC-5 KO kidneys. Endocytosis in the proximal tubule cells from KO mice was reduced compared with that in WT animals. Endocytosis in WT but not in KO cells was inhibited by bafilomycin A-1 and Cl(-) depletion, whereas endocytosis in both WT and KO cells was inhibited by the NHE3 blocker, S3226. Infection with adenovirus containing WT ClC-5 rescued receptor-mediated endocytosis in KO cells, whereas infection with any of the three disease-causing mutants, myc-W22G-ClC-5, myc-S520P-ClC-5, or myc-R704X-ClC-5, did not. WT and the three mutants all trafficked to the apical surface, as assessed by surface biotinylation. WT-ClC-5 and the W22G mutant were internalized similarly, whereas neither the S520P nor the R704X mutants was. These data indicate that ClC-5 is important for Cl(-) and proton pump-mediated endocytosis. However, not all receptor-mediated endocytosis in the proximal tubule is dependent on ClC-5. There is a significant fraction that can be inhibited by an NHE3 blocker. Our data from the mutants suggest that defective targeting and trafficking of mutant ClC-5 to the endosomes are a major determinant in the lack of normal endocytosis in Dent's disease.
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PMID:ClC-5: role in endocytosis in the proximal tubule. 1594 52