The role of aspartic and cysteine proteinases in albumin degradation by rat kidney cortical lysosomes

Baricos, William H.; Zhou, Youwen; Fuerst, Ronnie S.; Barrett, Alan J.; Shah, Sudhir V.

doi:10.1016/0003-9861(87)90625-4

Cited by 31 publications

(13 citation statements)

References 19 publications

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“…There was no significant change in the specific activity of cathepsin B (112% of controls) in the same cortical homogenates or in the specific activity of cathepsin L in livers obtained from the same rats (table 1). These data suggest that the increased activity of ca thepsin L does not result from a non-specific increase in tubular lysosomal enzyme activity and are in agreement with our previous obser vations concerning changes in the activity of renal tubular cathepsin D (another lysosomal proteinase important in tubular protein degra dation) [5] in response to an increased filtered protein load resulting from puromycin aminonucleoside-induced glomerulonephritis [11], The increase in cortical cathepsin L activity is also in agreement with previous reports by Ol- bricht et al [22, 23j who observed increased cysteine proteinase activity in tubules isolated from rats with experimentally induced protein uria.…”

Section: Cysteine Proteinoses and Renal Tubular Albumin Degradationsupporting

confidence: 92%

“…For determination of pH optima, albumin degrada tion was measured using ,:5I-labelled BSA as previously described [5]. For Km and ka, determination, the rate of albumin degradation was measured by the fluorescamine method [9], Km and k", were calculated by the method of Eisenthal and Cornish-Bowden 110).…”

Section: Albumin Degradation By Cathepsins B and Lmentioning

confidence: 99%

“…Several diverse lines of evidence indicate that cysteine proteinases may also play important roles in various aspects of renal pathophysiolo gy as well. For example, in a previously pub lished study [5], we presented evidence that cysteine proteinases play an important role in the lysosomal degradation of filtered protein by epithelial cells of the proximal tubule. In addition, recent evidence from this laboratory and others indicates that cysteine proteinases may also be involved in the increase in perme ability of the glomerular basement membrane (GBM) which occurs in glomerular disease.…”

Section: Introductionmentioning

confidence: 99%

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Role of Cathepsin B and L in Anti-Glomerular Basement Membrane Nephritis in Rats

Baricos¹,

Shah

1989

Kidney Blood Press Res

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We have examined the potential role of the cysteine proteinases, cathepsin B and L, in renal tubular protein degradation and increased permeability of the glomerular basement membrane (GBM) which occurs in a neutrophil- and complement-independent model of anti-GBM antibody disease. The specific activity of cathepsin L, but not cathepsin B was significantly increased (157%, p > 0.01) in cortical homogenates (85-90% tubules) prepared from anti-GBM-treated rats compared to saline-treated controls. Using highly purified cathepsin B and L, we documented the ability of these proteinases to degrade albumin in vitro (K_m 5.92 and 0.22 µM for B and L, respectively). In two separate studies, treatment of rats with trans-epoxysuccinyl-L-leucylamido-(4-guanidino)butane, (E-64), a specific and irreversible inhibitor of cysteine proteinases, significantly reduced proteinuria (-45 and -41%, p < 0.01) in the 24-hour period following injection of the anti-GBM IgG. Taken together, these data suggest an important role for cysteine proteinases in the increased tubular protein degradation which occurs in response to increased filtered protein loads and in the increased GBM permeability (proteinuria) characteristic of glomerular disease.

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Section: Cysteine Proteinoses and Renal Tubular Albumin Degradationsupporting

confidence: 92%

Section: Albumin Degradation By Cathepsins B and Lmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Role of Cathepsin B and L in Anti-Glomerular Basement Membrane Nephritis in Rats

Baricos¹,

Shah

1989

Kidney Blood Press Res

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“…Cathepsin D plays an important role in the lysosomal-mediated degradation of proteins [5]. It has a broad peptide bond specificity similar to pepsin and has been shown to be involved in various physiological pathways, such as intracellular catabolic proteolysis [6,7], extracellular proteolysis and processing, secretion and activation of enzymes and hormones [8].…”

Section: Introductionmentioning

confidence: 99%

Molecular characterization and expression analysis of the channel catfish cathepsin D genes

Feng

Zhang

Liu

et al. 2011

Fish & Shellfish Immunology

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“…The exact anatomical location of this 'degradation pathway' has not been determined but it is most likely to occur by endocytosis and lysosomal degradation in proximal tubule cells. Histochemical and electron microscopical studies [9] have shown that following endocytosis, larger molecular weight (MW) proteins are degraded within lysosomes of the epithelial cells in proximal convoluted tubules while 125 I-labeled BSA has been shown to be degraded by lysates of rat kidney lysosomes [10]. The degradation pathway appears to be nonspecific since all proteins tested to date have been shown to be degraded, including horseradish peroxidase, immunoglobulin G (IgG) and albumin [1][2][3][4][5][6][7], the extent of degradation varying from protein to protein.…”

Section: Introductionmentioning

confidence: 99%

Nephrotic-Like Proteinuria in Experimental Diabetes

Greive¹,

Osicka²,

Russo³

et al. 2002

Am J Nephrol

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Aims/Hypothesis: Streptozotocin (STZ) diabetic rats are characterized by the development of albuminuria. It is not known, however, whether the excess excretion of protein is primarily due to intact protein or protein fragments or whether it is specific for albumin or occurs for all high-molecular-weight plasma proteins. To test this we have measured the excretion rates and fractional clearances of [¹⁴C]albumin, [³H]immunoglobulin G and [³H]transferrin in diabetic rats. Methods: The radiolabeled proteins were delivered to the circulation of conscious diabetic (STZ induced for 6 weeks) and control rats by ALZET osmotic pumps. The plasma level of the radiolabeled proteins reached steady-state levels by day 7. Urine and plasma samples from day 7 were used to determine the excretion rates of the proteins by radioactivity and radioimmunoassay. Results: When excretion rates were determined by radioactivity it was apparent that only the albumin excretion rate increased significantly with STZ diabetes to a value of 354 ± 166 µg/min which agrees with proteinuria determined by Biuret assay of 299.9 ± 52.4 µg/min. The major proportion of protein being excreted was in the form of protein fragments which are not detected by conventional immmunochemical assays. Conclusion: The previously unrecognized nephrotic-like levels of proteinuria in experimental diabetes appears to be associated with an albumin-specific mechanism responsible for the increase in albumin peptides in urine. There was significant lowering of plasma albumin concentration but plasma concentrations of transferrin and immunoglobulin G remained unchanged. There was also no significant appearance of intact protein in urine that is normally found in nephrotic states.

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The role of aspartic and cysteine proteinases in albumin degradation by rat kidney cortical lysosomes

Cited by 31 publications

References 19 publications

Role of Cathepsin B and L in Anti-Glomerular Basement Membrane Nephritis in Rats

Role of Cathepsin B and L in Anti-Glomerular Basement Membrane Nephritis in Rats

Molecular characterization and expression analysis of the channel catfish cathepsin D genes

Nephrotic-Like Proteinuria in Experimental Diabetes

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