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Protease activity of plasma hemopexin
Winston W Bakker1, Theo Borghuis, Martin C Harmsen
1Department of Pathology and Laboratory Medicine, and Department of Pediatrics, University Hospital Groningen, Groningen, The Netherlands. w.w.bakker@path.umcg.nl
Kidney International
|July 15, 2005
Summary
Hemopexin, a plasma protein, acts as a toxic protease causing kidney damage and proteinuria characteristic of minimal change nephrotic syndrome in rats. This study confirms hemopexin
Area of Science:
- Nephrology
- Molecular Biology
- Biochemistry
Background:
- Plasma hemopexin is implicated in minimal change nephrotic syndrome pathogenesis.
- Previous studies showed hemopexin infusion causes glomerular lesions and proteinuria in rats.
- The protease activity of hemopexin was suspected but not confirmed to be intrinsic.
Purpose of the Study:
- To confirm if hemopexin itself possesses protease activity.
- To investigate the role of hemopexin as a toxic protease in nephrotic syndrome.
Main Methods:
- Recombinant hemopexin was produced and compared to plasma hemopexin.
- Protease activity was assessed using Western blotting, in vitro assays, and kidney tissue incubation.
- Proteinuria induction was tested in rats using unilateral renal perfusion with recombinant hemopexin.
Main Results:
- Recombinant hemopexin showed identical identity and protease activity to plasma hemopexin.
- Hemopexin degraded glomerular ectoapyrase and sialoglycoproteins, an effect inhibited by protease inhibitors.
- Recombinant hemopexin induced significant proteinuria in rats, unlike heat-inactivated versions.
Conclusions:
- Hemopexin molecule possesses intrinsic protease activity.
- Hemopexin acts as a toxic protease, causing proteinuria and glomerular changes in minimal change nephrotic syndrome models.