Morphine modulates cathepsin B and L activity in isolated glomeruli and mesangial cells
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P C Singhal1, S Sagar, N Gibbons
1Department of Medicine, Long Island Jewish Medical Center, New Hyde Park, New York 10042.
Abstract:
Altered matrix degradation may be playing a role in the development of initial mesangial expansion and subsequent glomerulosclerosis in persons with heroin abuse. We studied whether morphine, a metabolite of heroin, had any effect on lysosomal content of cathepsin B and L in mesangial cells. Morphine (10(-6) M) increased (P < 0.01) mesangial cathepsin B and L activity (control, 22.1 + 2.2 vs. morphine, 31.4 + 1.4 mol NMec/microgram protein, N = 5). Morphine (10(-6) M) also increased (P < 0.01) glomerular cathepsin B and L activity (control, 0.1 + 0.01 vs. morphine, 2.2 +/- 0.2 pmol NMec/microgram protein, N = 3). This effect of morphine occurred in a dose-dependent manner. These results suggest that morphine enhances cathepsin B and L activity in mesangial cells and isolated glomeruli. This effect of morphine may enhance capacity of mesangial cells to degrade increased amount of mesangial macromolecules.
Insights
Morphine, a heroin metabolite, boosts cathepsin B and L activity in kidney mesangial cells and glomeruli. This suggests a mechanism for heroin-induced kidney damage through enhanced matrix degradation.
Area of Science:
- Nephrology
- Cell Biology
- Pharmacology
Background:
- Altered matrix degradation is implicated in glomerulosclerosis development in heroin users.
- Heroin abuse can lead to kidney damage, including mesangial expansion and glomerulosclerosis.
Purpose of the Study:
- To investigate the effect of morphine, a primary heroin metabolite, on lysosomal cathepsin B and L activity.
- To determine if morphine influences matrix-degrading enzymes in kidney mesangial cells and glomeruli.
Main Methods:
- Cultured human mesangial cells were treated with morphine (10^-6 M).
- Lysosomal cathepsin B and L activity was measured in mesangial cells and isolated glomeruli.
- Dose-dependent effects of morphine were assessed.
Main Results:
- Morphine significantly increased cathepsin B and L activity in mesangial cells (P < 0.01).
- Morphine also significantly elevated cathepsin B and L activity in isolated glomeruli (P < 0.01).
- The observed increase in enzyme activity was dose-dependent.
Conclusions:
- Morphine enhances cathepsin B and L activity in kidney mesangial cells and glomeruli.
- This morphine-induced increase in enzyme activity may contribute to enhanced mesangial cell capacity for matrix degradation.
- These findings suggest a potential mechanism linking heroin use to kidney pathology via matrix remodeling.