scholarly journals Increased cathepsin D-like activity in cortex, tubules, and glomeruli isolated from rats with experimental nephrotic syndrome

1984 ◽  
Vol 223 (2) ◽  
pp. 393-399 ◽  
Author(s):  
W H Baricos ◽  
S V Shah
Keyword(s):  
Nephrotic Syndrome ◽  
Cathepsin D ◽  
Rat Kidney ◽  
Urinary Protein Excretion ◽  
Urinary Protein ◽  
Rat Tissues ◽  
Puromycin Aminonucleoside ◽  
Protein Excretion ◽  
Normal Rat ◽  
Functional Areas

We have examined the activity and distribution of cathepsin D (EC 3.4.23.5), a major renal lysosomal endoproteinase, in the various anatomical and functional areas of normal rat kidney. Cathepsin D-like activities (delta A280/h per mg of protein) in normal rat tissues were: cortex, 0.78 +/- 0.05, n = 37; medulla, 0.62 +/- 0.03, n = 12; papilla, 0.63 +/- 0.04, n = 12; tubules, 0.74 +/- 0.04, n = 28; glomeruli, 0.59 +/- 0.03, n = 28; and liver, 0.41 +/- 0.02, n = 28. Enzyme activity was maximal at pH 3.0-3.5 and inhibited more than 90% by pepstatin (6.7 micrograms/ml), suggesting that the enzyme is cathepsin D. In subsequent experiments we measured cathepsin D-like activity in cortex, tubules and glomeruli isolated from rats with puromycin aminonucleoside (PAN)-induced nephrotic syndrome. Treated animals (15 mg of PAN/100g body wt., intraperitoneally) developed proteinuria beginning 4 days after injection and exceeding 900 mg/24h on day 9. In two separate experiments involving 52 animals we observed a significant increase in cathepsin D-like activity in cortex (+82.7%), tubules (+109.6%) and glomeruli (+54.7%) isolated from PAN-treated rats killed during marked proteinuria (day 9, mean total urinary protein excretion: 937 +/- 94 mg/24h). This increase was observed whether the activity was expressed per mg of DNA or per mg of protein. Increased cathepsin D-like activity was first observed in cortex and tubules coincident with the onset of proteinurea (day 4, mean total urinary protein excretion: 112 +/- 23 mg/24h). In contrast with the significant elevation of renal cathepsin D-like activity, the activity (nmol/h per mg of protein) of alpha-L-fucosidase (EC 3.2.1.51), a non-proteolytic enzyme, was markedly decreased in the identical samples used for the measurement of cathepsin D-like activity: cortex (-46.4%); tubules (-46.1%); and glomeruli (-38.5%). In addition to changes in renal enzyme activities, PAN-treated rats excreted large amounts of cathepsin D-like activity in their urine (beginning on day 3) compared with nearly undetectable cathepsin D-like activity in the urine from control rats. The significant increases in glomerular and tubular cathepsin D activity may reflect an important role for this enzyme in the pathophysiology associated with PAN-induced nephrotic syndrome.

Acute Effects of Ciclosporin on Renal Hemodynamics and Urinary Protein Excretion in Patients with the Nephrotic Syndrome

Nephron ◽  
1991 ◽  
Vol 59 (3) ◽  
pp. 369-374 ◽  
Author(s):  
Giorgio Fuiano ◽  
Giuseppe Conte ◽  
Vincenzo Sepe ◽  
Mario Balletta ◽  
Paola Cianfrone ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Renal Hemodynamics ◽  
Urinary Protein Excretion ◽  
Urinary Protein ◽  
Acute Effects ◽  
Protein Excretion

scholarly journals Platelet-activating factor mediates angiotensin II-induced proteinuria in isolated perfused rat kidney.

1997 ◽  
Vol 8 (9) ◽  
pp. 1391-1398
Author(s):  
N Perico ◽  
R Lapinski ◽  
K Konopka ◽  
S Aiello ◽  
M Noris ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Receptor Antagonist ◽  
Rat Kidney ◽  
Platelet Activating Factor ◽  
Urinary Protein Excretion ◽  
Urinary Protein ◽  
Isolated Kidney ◽  
Protein Excretion ◽  
Paf Receptor ◽  
Paf Receptor Antagonist

Isolated kidney preparations (IPK) from male Sprague Dawley rats perfused at constant pressure were used to evaluate the effect of angiotensin II (AII) and platelet-activating factor (PAF) on renal function and urinary protein excretion. Compared with basal, intrarenal infusion of AII at 8 ng/min caused a progressive increase in protein excretion (11 +/- 6 versus 73 +/- 21 micrograms/min) in parallel with a decline in renal perfusate flow (RPF) (29 +/- 3 versus 18 +/- 3 ml/min). Addition to the perfusate of PAF at 50 nM final concentration also induced proteinuria (9 +/- 4 versus 55 +/- 14 micrograms/min) but did not change RPF (29 +/- 3 versus 30 +/- 3 ml/min). Preexposure of isolated kidneys to the PAF receptor antagonist WEB 2086 prevented the increase in urinary protein excretion induced by AII infusion (basal: 13 +/- 6; post-AII: 12 +/- 7 micrograms/min) but failed to prevent the vasoactive effect of AII (RPF, basal: 30 +/- 2; post-AII: 21 +/- 3 ml/min). In additional experiments, dexamethasone reduced the proteinuric effect of PAF remarkably. These results indicate that in isolated kidney preparation: (1) AII infusion induced proteinuria and decreased RPF; and (2) the effect of AII in enhancing urinary protein excretion was completely prevented by a specific PAF receptor antagonist, which, however, did not influence the AII-induced fall in RPF. It is suggested that PAF plays a major role in AII-induced changes in the permselective function of the glomerular capillary barrier.

scholarly journals Angiotensin II modulates glomerular capillary permselectivity in rat isolated perfused kidney.

1996 ◽  
Vol 7 (5) ◽  
pp. 653-660 ◽  
Author(s):  
R Lapinski ◽  
N Perico ◽  
A Remuzzi ◽  
F Sangalli ◽  
A Benigni ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Excretion Rate ◽  
Rat Kidney ◽  
Renin Angiotensin System ◽  
Urinary Protein Excretion ◽  
Urinary Protein ◽  
Converting Enzyme Inhibitors ◽  
Glomerular Capillary ◽  
Protein Excretion ◽  
Fractional Clearance

Studies in experimental animals and humans have documented that inhibition of the renin-angiotensin system by angiotensin-converting enzyme inhibitors reduces urinary protein excretion rate and retards the development of renal injury. Here we sought to investigate whether angiotensin II (All) modified the size-selective properties to macromolecules of the glomerular capillary barrier in isolated perfused rat kidney preparation. Compared with basal values, continuous All infusion into the renal artery at the rate of 3 or 8 ng/min, but not at 0.6 ng/min, induced a progressive and significant increase in urinary protein excretion rate. Evaluation of the sieving properties of the glomerular barrier by fractional clearance of polydisperse Ficoll showed that All significantly enhanced the filtration of tracer molecules of radil > or = 34A. All-induced changes in urinary protein excretion rate and in Ficoll fractional clearance were completely prevented by pretreatment with the specific All Type 1 receptor antagonist SR 47436.

scholarly journals Renal neuraminidase. Characterization in normal rat kidney and measurement in experimentally induced nephrotic syndrome

1986 ◽  
Vol 239 (3) ◽  
pp. 705-710 ◽  
Author(s):  
W H Baricos ◽  
S Cortez-Schwartz ◽  
S V Shah
Keyword(s):  
Nephrotic Syndrome ◽  
Specific Activity ◽  
Rat Kidney ◽  
Puromycin Aminonucleoside ◽  
Glomerular Diseases ◽  
Neuraminidase Activity ◽  
Acetylneuraminic Acid ◽  
Normal Rat ◽  
High Concentrations ◽  
Triton X

Several lines of evidence suggest that increased neuraminidase activity may be responsible for the loss of glomerular N-acetylneuraminic acid (AcNeu) observed in various glomerular diseases. However, virtually no information is available on the activity of neuraminidase in glomeruli or the potential role of this enzyme in glomerular pathophysiology. Utilizing 2′-(4-methylumbelliferyl)-alpha-D-N-acetylneuraminic acid (4MU-AcNeu) as substrate, we defined optimal assay conditions and characterized neuraminidase activity in glomeruli and, for comparison, in other renal fractions and liver. Neuraminidase activity in glomeruli, cortex and tubules was maximal at pH 4.4. The Km for 4MU-AcNeu was estimated to be 195 microM for glomeruli and 226 microM for cortex. Glomerular neuraminidase was inhibited by AcNeu (90% at 25 mM) and high concentrations of Triton X-100 (26% at 0.5%), but unaffected by CaCl2, EDTA or N-ethylmaleimide (each 1 mM). Neuraminidase activity (nmol/h per mg of protein; mean +/- S.E.M.) in normal rat kidney was: cortex, 14.47 +/- 0.76; medulla, 7.85 +/- 0.64; papilla, 2.64 +/- 0.11; tubules, 13.79 +/- 0.70; glomeruli, 5.57 +/- 0.28. In comparison, neuraminidase activity in rat liver was 2.58 +/- 0.14. Puromycin aminonucleoside (PAN)-induced nephrotic syndrome is a model of glomerular disease in which the loss of glomerular AcNeu is well documented. In two separate studies, we observed no change in the specific activity of neuraminidase in either glomeruli or cortex isolated from rats treated with PAN (15 mg/100 g, intraperitoneally) and killed at either the onset or the peak of proteinuria. Results were similar whether neuraminidase activity was expressed per mg of protein or per microgram of DNA.

Mizoribine Reduces Urinary Protein Excretion in Rats Given Puromycin Aminonucleoside

1996 ◽  
Vol 16 (2) ◽  
pp. 167-172 ◽  
Author(s):  
T. Shibasaki ◽  
H. Matsuda ◽  
H. Gomi ◽  
M. Usui ◽  
F. Ishimoto ◽  
...  
Keyword(s):  
Urinary Protein Excretion ◽  
Urinary Protein ◽  
Puromycin Aminonucleoside ◽  
Protein Excretion

scholarly journals Antioxidants protect podocyte foot processes in puromycin aminonucleoside-treated rats.

1994 ◽  
Vol 4 (12) ◽  
pp. 1974-1986
Author(s):  
S D Ricardo ◽  
J F Bertram ◽  
G B Ryan
Keyword(s):  
Electron Microscopy ◽  
Scanning Electron Microscopy ◽  
Epithelial Cell ◽  
Urinary Protein Excretion ◽  
Urinary Protein ◽  
Alpha Tocopherol ◽  
Puromycin Aminonucleoside ◽  
Glomerular Epithelial Cell ◽  
Protein Excretion ◽  
Scanning Electron

Whether a reduction in urinary protein excretion in rats coadministered puromycin aminonucleoside and antioxidants was associated with a reduction in alterations to glomerular epithelial cell (podocyte) ultrastructure was examined. Daily urinary protein excretion was measured in rats that received a single i.v. injection of saline or puromycin aminonucleoside with or without coadministration of antioxidants. The coadministration of alpha-tocopherol/ascorbic acid, dimethyl thiourea, or superoxide dismutase to puromycin aminonucleoside-treated rats reduced proteinuria by approximately 90, 40, and 60%, respectively, over the 18-day period studied. For a second group of rats, daily urinary protein excretion was measured and kidneys were processed for light microscopy and transmission and scanning electron microscopy 4, 5, and 10 days after injection. Transmission electron microscopic morphometric analysis of glomeruli from puromycin aminonucleoside-treated rats coadministered antioxidants revealed significantly reduced foot process effacement on Days, 4, 5, and 10 compared with rats that received puromycin aminonucleoside alone. Thus, at Day 10, puromycin aminonucleoside-treated rats coadministered alpha-tocopherol/ascorbic acid, dimethyl thiourea, or superoxide dismutase contained 90, 74, and 88% (P < 0.01 in all cases) more glomerular epithelial cell filtration slits per unit length of glomerular basement membrane than rats treated with puromycin aminonucleoside alone. In contrast, by scanning electron microscopy, the antioxidants were found to provide no protection against the changes occurring in glomerular epithelial cell bodies and major processes. These results provide further evidence of a role for reactive oxygen species in puromycin aminonucleoside nephrosis and indicate that the antioxidants provide protection against the changes occurring in glomerular epithelial cell foot processes.

scholarly journals Chinese Herbal Injections for Primary Nephrotic Syndrome in Adults: A Systematic Review and Network Meta-Analysis

2020 ◽  
Vol 2020 ◽  
pp. 1-11 ◽  
Author(s):  
Shisheng Han ◽  
Tianwen Yao ◽  
Yanhua Lu ◽  
Yan Lu ◽  
Yanqiu Xu ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Serum Albumin ◽  
Remission Rate ◽  
Meta Analysis ◽  
Urinary Protein Excretion ◽  
Urinary Protein ◽  
Primary Nephrotic Syndrome ◽  
Chinese Herbal ◽  
Protein Excretion ◽  
Total Remission

Primary nephrotic syndrome (PNS) is a common renal disease that presents with heavy proteinuria and hypoalbuminemia. Despite notable advances in its treatment, some patients show poor responses and clinical outcomes when treated with conventional Western medicine (WM). Chinese herbal injections (CHIs) have been reported to have beneficial effects for PNS. The aim of the present study was to comprehensively determine the efficacy and safety of CHIs for PNS in adults using a network meta-analysis approach. PubMed, Embase, the Cochrane library, and four Chinese databases were systematically searched to identify randomized controlled trials (RCTs) using CHIs for treatment of PNS published before June 1, 2019. Quality assessment of the identified RCTs was performed according to the Cochrane Handbook. Pooled odds ratios (OR) or mean differences (MD) with corresponding 95% confidence intervals (CI) were calculated for discrete or continuous variables, respectively. The primary outcome was complete/total remission and secondary outcomes were serum albumin and urinary protein excretion. The surface under the cumulative ranking curve (SUCRA) value and cluster analyses were used to rank treatment by probability. Eighty-five studies involving 11 CHIs and 5801 subjects were included. Compared with WM alone, CHI plus WM showed an improved complete/total remission rate as well as higher serum albumin and lower 24-hour urinary protein excretion, except in the following: Yinxingye injection plus WM did not improve the total remission rate, and Dengzhanhua or Xueshuantong injection plus WM did not lower the 24-hour urinary protein excretion. Either Danhong (DH) or Dengzhanhua (DZH) injection plus WM was the preferable treatment for PNS based on SUCRA and cluster analyses of clinical remission and adverse events. However, considering that literature in this area is limited, these results need further validation. CHIs administered as adjuvants to WM showed favourable outcomes for PNS. DH + WM and DZH + WM might be the potential optimal therapies for PNS.

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