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Meprin activity in rats with experimental renal disease
H Trachtman1, R Greenwald, S Moak
1Department of Pediatrics (Division of Nephrology), Schneider Children's Hospital, New Hyde Park, NY 11042.
Abstract:
Activity of renal meprin, a membrane-bound proteinase in the proximal tubule brush border, was measured in normal rats and in two disease groups: chronic puromycin aminonucleoside nephropathy for 12 weeks and streptozocin-induced diabetes for 6 months. Enzyme activity in kidney homogenates was assayed using azocasein as substrate. The mean activity of mephrin was 3.22 +/- 0.34 U/g kidney weight in normal rats. In diabetic animals, enzyme activity was 8.58 +/- 2.11 U/g kidney weight, P < 0.01. In contrast, meprin activity was decreased in rats with puromycin-induced glomerulopathy, 2.13 +/- 0.17 U/g kidney weight, P < 0.01. These findings indicate that meprin activity is elevated in experimental diabetes. Diminished activity of this luminal membrane enzyme in puromycin aminonucleoside nephropathy may contribute to renal injury in this disease model associated with massive urinary protein excretion.
Insights
Renal meprin (enzyme) activity significantly increases in experimental diabetes but decreases in puromycin-induced nephropathy, suggesting roles in kidney disease progression.
Area of Science:
- Nephrology
- Biochemistry
- Enzymology
Background:
- Meprin is a membrane-bound proteinase located in the proximal tubule brush border of the kidney.
- Its role in kidney disease pathogenesis is not fully understood.
Purpose of the Study:
- To investigate the activity of renal meprin in experimental models of diabetic nephropathy and puromycin aminonucleoside nephropathy.
- To determine if meprin activity correlates with renal injury in these disease states.
Main Methods:
- Kidney homogenates from normal, diabetic (streptozocin-induced), and puromycin aminonucleoside nephropathy rats were analyzed.
- Enzyme activity of meprin was quantified using azocasein as a substrate.
Main Results:
- Meprin activity was significantly elevated in streptozocin-induced diabetic rats (8.58 U/g kidney weight) compared to normal rats (3.22 U/g kidney weight).
- Conversely, meprin activity was significantly decreased in puromycin aminonucleoside nephropathy rats (2.13 U/g kidney weight) compared to normal rats.
- These changes were statistically significant (P < 0.01).
Conclusions:
- Renal meprin activity is markedly elevated in experimental diabetes.
- Reduced meprin activity in puromycin aminonucleoside nephropathy may contribute to renal injury and massive proteinuria.
- Meprin activity serves as a potential biomarker for distinct kidney disease pathologies.