Decreased Proteinase Activity in Isolated Glomeruli of Streptozotocin Diabetic Rats

Teschner, Markus; Schaefer, Roland M.; Svarnas, Alexandra; Heidland, Ulrich E.; Heidland, A.

doi:10.1159/000168014

Cited by 30 publications

(24 citation statements)

References 12 publications

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“…Alterations in cathepsin activity were described in 1983 by Mohanam and Bose [16]. Teschner et al [17] subsequently found decreased glomerular proteinase (azocaseinase) activity in this model. Since metalloproteinases have no activity against azocasein, it is likely that cathepsin activity was being measured in this study.…”

Section: Discussionmentioning

confidence: 56%

Decreased Glomerular Proteinase Activity in the Streptozotocin Diabetic Rat

Song

Singh²,

Leehey³

1999

Am J Nephrol

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Decreased glomerular proteinase activity may contribute to matrix accumulation in diabetes. Male Sprague-Dawley rats were rendered diabetic by injection of streptozotocin (STZ) 65 mg/kg i.v.; age-matched, sham-injected rats served as controls. Glomeruli from diabetic rats 1 month after STZ injection demonstrated significant decreases in collagenase and cathepsin B activities compared to control glomeruli. Treatment with insulin resulted in a slight (but not significant) increase in collagenase activity and normalized cathepsin B activity. We conclude that decreased glomerular collagenase and cathepsin B activities are present in STZ diabetes. These alterations may contribute to mesangial matrix accumulation.

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Section: Discussionmentioning

confidence: 56%

Decreased Glomerular Proteinase Activity in the Streptozotocin Diabetic Rat

Song

Singh²,

Leehey³

1999

Am J Nephrol

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“…Moreover, several investigators have examined MMP activity in diabetic models. Reckelhoff et al [30]described decreased glomerular metalloproteinase and Teschner et al [31]found decreased glomerular proteinase activity in diabetic rats. Nakamura et al [32]demonstrated diminishing levels of MMP-3 with age in glomeruli of streptozotocin-induced diabetic rats.…”

Section: Discussionmentioning

confidence: 99%

Renal in situ Hybridization Studies of Extracellular Matrix Related Molecules in Type 1 Diabetes mellitus

Suzuki

Yagame

Kim

et al. 2002

Nephron

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Background/Aim: Progressive expansion of mesangial matrix and glomerular basement membrane thickening represent alterations in the balance between synthesis and degradation of glomerular extracellular matrix (ECM) protein and are hallmarks of diabetic nephropathy. In order to elucidate the basis for this imbalance between the synthesis and the degradation of ECM in renal tissues from patients of type 1 diabetes mellitus (type 1D) with diabetic nephropathy (DN), we examined the expression of α1 chain of type IV collagen (IV-C), matrix metalloproteinase-2 and -3 (MMP-2, MMP-3), tissue inhibitor of metalloproteinase-1 (TIMP-1) and β-actin mRNA using a high-resolution in situ hybridization with digoxigenin-labeled oligonucleotide. Methods: Patients were divided into two groups based on both of degree of mesangial expansion using electron microscopic point counting morphometric methods and duration of type 1D: 7 ‘fast-track’ patients were selected for their very rapid development of DN structural changes and 8 ‘slow-track’ patients for their very slow development of DN structural changes. Seven normal human kidney (NHK) tissues were used as controls. Results: Positive cells for each mRNA were observed in glomerular resident cells, including glomerular mesangial, epithelial and endothelial cells and cells of Bowman’s capsule. The percentage of glomerular cells positive for IV-C, MMP-2 and MMP-3 mRNA was significantly greater in the ‘slow-track’ vs. ‘fast-track’ patients. No significant differences in percentage positive cells was seen for β-actin mRNA. Furthermore, to elucidate the total number of positive cells per glomerulus for each mRNA, we estimated total cell number of glomerulus using morphometric techniques on light microscopy tissues. The total cell number per glomerulus was significantly greater in ‘fast-track’ than that in ‘slow-track’ patients and NHK. The total number of positive cells per glomerulus for MMP-2 in NHK was significantly greater than that in ‘slow-track’ and ‘fast-track’ patients. Conclusion: Thus, IV-C, MMP-2, MMP-3 and TIMP-1 mRNA are expressed in resident glomerular cells in renal tissues from NHK and type 1D. Glomerular alterations in these in situ mRNA expressions sufficient to explain ECM accumulation and DN risk were not uncovered. These largely negative results could be due to methodologic quantitative imprecision or could indicate that post-translational differences account for ECM imbalance in DN. However, these studies make it clear that unraveling the nature of the ECM production/removal imbalance in DN will require careful consideration of alterations in glomerular cell number.

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“…There is much evidence to suggest that the renal degradation of filtered proteins occurs in the lysosomes of the proximal tubules and lysosomal activity and/or trafficking to the lysosomes has been shown to decrease with the progression of experimental diabetes [5][6][7][35][36][37][38]. A reduction in the lysosomal activity/trafficking would account for the reduction in the degradation of IgG and transferrin, and the apparent increase in FC by RIA, with no increase in the glomerular sieving.…”

Section: Discussionmentioning

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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Decreased Proteinase Activity in Isolated Glomeruli of Streptozotocin Diabetic Rats

Cited by 30 publications

References 12 publications

Decreased Glomerular Proteinase Activity in the Streptozotocin Diabetic Rat

Decreased Glomerular Proteinase Activity in the Streptozotocin Diabetic Rat

Renal in situ Hybridization Studies of Extracellular Matrix Related Molecules in Type 1 Diabetes mellitus

Nephrotic-Like Proteinuria in Experimental Diabetes

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