Altered activity of plasma hemopexin in patients with minimal change disease in relapse

Abstract

Since an active isoform of plasma hemopexin (Hx) has been proposed to be a potential effector molecule in minimal change disease (MCD), we tested plasma and urine samples from subjects with MCD in relapse (n = 18) or in remission (n = 23) (after treatment with prednisolone) for presence or activity of Hx. For comparison, plasma or urine from proteinuric subjects with focal and segmental glomerulosclerosis (FSGS, n = 11), membranoproliferative glomerulonephritis (MPGN, n = 9), IgA nephropathy (n = 5) or healthy control donors (n = 10), were incorporated into the study. Electrophoresis and Western blotting methods were used for evaluation of the Hx status, whereas protease activity of Hx was tested upon kidney tissue in vitro according to standard methods. The results show (1) a decreased mean titer of plasma Hx exclusively in MCD relapse subjects as compared with MCD in remission (0.21+/-0.14 mg/ml vs 0.44+/-0.06 mg/ml; p < 0.01). Mean Hx titers in other proteinuric subjects ranged from 0.38+/-0.05 mg/ml to 0.40+/- 0.06 mg/ml, whereas, the mean titer of healthy controls was 0.59+/-0.03 mg Hx/ml; (2) an increased Hx activity (expressed in arbitrary units) exclusively in plasma from MCD relapse subjects (3.3+/-0.72 vs 1.16+/-0.56, MCD remission; p < 0.01); (3) different Western blot patterns in MCD relapse vs remission plasma; (4) reduced stainability or virtual absence of the 80-kD Hx band in blots of urine from MCD relapse in contrast to urine samples from other proteinuric subjects with FSGS, MPGN, or IgA nephropathy. It is concluded that Hx in MCD relapse subjects may exist in an altered isoform, showing enhanced protease activity as compared with subjects in remission, subjects with other forms of primary glomerulopathy, or healthy control individuals.

Comprehensive and quantitative proteome profiling of the mouse liver and plasma

“…The remaining reported concentrations were obtained from the literature as referenced: interleukin-3 28 ; CSF1 29 ; PLAU 30 ; beta-enolase 31 ; enolase 1, alpha 32 ; IGF1 33 ; uromodulin 34 ; lactotransferrin 35 ; HGFAC, serum amyloid A protein, IGFALS, factor XII, apolipoprotein C-II 4 ; beta-2-microglobulin 36 ; PROZ 37 ; protein C 38 ; apolipoprotein D 39 ; apolipoprotein C-III 40 ; vitamin D-binding protein 41 ; alpha-2-HS-glycoprotein 42 ; hemopexin. 43 teins were common to both data sets and corresponded to 25.6% of the proteins identified in the liver tissue and to 38.5% of the proteins identified in plasma (Fig. 5A).…”

Circulating Permeability Factors in Idiopathic Nephrotic Syndrome and Focal Segmental Glomerulosclerosis

“…Injection into rats causes proteinuria and glomerular alterations characteristic of MCNS (15). It is found in the urine of children with steroid-responsive NS and disappears during remission (16). Studies of VPR and hemopexin in patients with FSGS have not been reported.…”

Purified and Recombinant Hemopexin: Protease Activity and Effect on Neutrophil Chemotaxis

“…Some prior studies have suggested that Hx might have intrinsic protease activity. Bakker et al identified a plasma factor 100 KF that is closely related to Hx and has protease activity that induced transient protein leakage after incubation with rat kidney ex vivo and perfusion of kidney (22,23). In a different study, protease activity was reported in recombinant Hx expressed in Pichia pastoris using an amidolytic assay, although there was no expressed control protein reported (24).…”

“…However, questions have been raised as to the safety of Hx infusion because of possible protease activity of Hx (22)(23)(24) and possible effects of Hx on neutrophil chemotaxis in a different study (25).…”