Molecular characterization of β-trace protein in human serum and urine: a potential diagnostic marker for renal diseases

Abstract

We have isolated beta-trace protein from cerebrospinal fluid, serum, plasma, and urine samples of normal volunteers and sera and hemofiltrate of patients with chronic renal failure. Blood-derived and urinary beta-trace have significantly higher molecular weights than their cerebrospinal fluid counterpart, the amino acid sequences being identical. Oligosaccharide structural analysis revealed these molecular weight differences to be due to different N-glycosylation. beta-Trace from hemofiltrate and urine has larger sugar chains and concurrently significantly higher sialylation than cerebrospinal fluid-beta-trace which bears truncated "brain-type" oligosaccharide chains (published previously). beta-Trace concentrations were about 40 ng/ml for normal sera and plasma. 2000-6000 ng/ml were measured in sera of dialysis patients whereas in normal human cerebrospinal fluid, beta-trace concentration was about 8000 ng/ml. A reduced amount of 900 ng/ml was found in a single case of hydrocephalus cerebri. The sialylated glycoforms of beta-trace detected in the blood are presumably derived from resorbed cerebrospinal fluid protein whereas beta-TP-molecules bearing asialo-oligosaccharides are absent due to their hepatic clearance. The residual, sialylated beta-TP-species are probably eliminated from the blood via the kidney. This physiological clearance mechanism for the sialylated glycoforms is disturbed in hemodialysis patients resulting in about 100-fold elevated serum concentrations. These results let us suggest beta-trace may become a useful novel diagnostic protein in renal diseases.

Serum β-Trace Protein and Risk of Mortality in Incident Hemodialysis Patients

“…However, it is certainly possible that there may be non-GFR determinants of serum BTP, and large studies in populations with measured GFR may be able to address this important question. BTP glycoforms lacking N-acetylneuraminic acid residues are rapidly removed by liver, and the remaining are excreted in the urine (36). Similar to cystatin C and other low molecular weight proteins, BTP is freely filtered by the glomerulus, and it is completely reabsorbed and metabolized by the proximal tubule (37).…”

Identification of Putative Gene Based Markers of Renal Toxicity

“…NGAL protein has been identified as a complex with matrix metalloproteinases in urine of patients with cancer (Yan et al 2001). Lipocalin-type prostaglandin D synthase (also known as L-PGDS or β-trace) is another member of the lipocalin family (Hoffmann et al 1993;Nagata et al 1991), and elevated serum and urinary levels of β-trace (L-PGDS) have been observed in patients with renal failure (Hoffmann et al 1997;Melegos et al 1999). L-PGDS is a secretory glycoprotein that catalyzes the isomerization of a precursor of prostanoids, prostaglandin (PG) H2, to produce prostaglandin D-2 (Urade and Hayaishi 2000).…”

The Cytoplasmic, Transmembrane, and Stem Regions of Glycosyltransferases Specify Their in Vivo Functional Sublocalization and Stability in the Golgi

“…An almost identical ␤-TP expression of all cell lines (0.5-1 g/10 6 confluent cells/48 h) was verified by Western blotting analysis of supernatants and by comparing the signal intensity with that of different concentrations of a known purified standard ␤-TP preparation from recombinant BHK-21 cells (25), using a monoclonal antibody raised against human ␤-TP (26, 49). About 0.5 mg of the reporter glycoprotein ␤-TP was quantitatively recovered from 500 -1000 ml of culture supernatant from each cell line by quantitative immunoaffinity purification (25,26), and detailed N-glycan mapping of each ␤-TP preparation was performed as described (17,25).…”