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Enhanced glomerular phospholipase activity in the obstructed kidney
A Fukuzaki1, J Morrissey, S Klahr
1Department of Medicine, Washington University School of Medicine St. Louis, Missouri, USA.
International Urology and Nephrology
|January 1, 1995
Summary
Kidney obstruction increases specific phospholipase enzymes, PE-specific PLA2 and PLC, in glomeruli. This enhanced enzyme activity contributes to increased eicosanoid production in obstructed kidneys, potentially aiding compensatory responses.
Area of Science:
- Nephrology
- Biochemistry
- Molecular Biology
Background:
- Glomerular eicosanoid production is implicated in kidney hemodynamic changes during obstruction.
- The precise mechanisms driving enhanced glomerular eicosanoid synthesis in obstructed kidneys remain unclear.
Purpose of the Study:
- To investigate the activities of key enzymes involved in eicosanoid production in isolated glomeruli from rats with unilateral ureteral obstruction (UUO) or bilateral ureteral obstruction (BUO).
- To elucidate the role of phospholipase A2 (PLA2) and phospholipase C (PLC) in mediating enhanced glomerular eicosanoid synthesis during kidney obstruction.
Main Methods:
- Isolated glomeruli were obtained from rats subjected to 24-hour UUO or BUO.
- Phospholipase A2 (PLA2) activity was measured by monitoring radiolabeled arachidonate release from phosphatidylcholine (PC) or phosphatidylethanolamine (PE) substrates.
- Phospholipase C (PLC) activity was assessed by quantifying the release of inositol triphosphate ([3H] IP3) from phosphatidylinositol 4,5 biphosphate ([3H] IP2).
Main Results:
- PE-specific PLA2 activity was significantly elevated in glomeruli from kidneys with BUO and the contralateral kidney of UUO (CLK).
- PLC activity was markedly increased in the cytosolic fraction of glomeruli from kidneys with UUO, BUO, and CLK compared to controls.
- PC-specific PLA2 activity showed no significant increase in any experimental group.
Conclusions:
- Enhanced activities of PE-specific PLA2 and PLC in glomeruli mediate the increased eicosanoid synthesis observed in obstructed kidneys.
- Elevated phospholipase activities in glomeruli from the CLK suggest a potential compensatory mechanism in response to unilateral obstruction.