Molecular characterization of beta-trace protein in human serum and urine: a potential diagnostic marker for renal diseases.
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.
Hoffmann
A
A
Gesellschaft für Biotechnologische Forschung, Department of Molecular Biology, Braunschweig, Germany.
Nimtz
M
M
Conradt
H S
HS
D000595:Amino Acid Sequence; D001609:Beta-Globulins / Q000032:analysis* / Q000737:chemistry / Q000652:urine; D015415:Biomarkers; D002236:Carbohydrate Conformation; D006031:Glycosylation; D006801:Humans; D019746:Intramolecular Oxidoreductases; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000652:urine*; D054834:Lipocalins; D008969:Molecular Sequence Data; D008970:Molecular Weight; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D009844:Oligosaccharides / Q000737:chemistry; D011134:Polysaccharides / Q000032:analysis / Q000737:chemistry; D012016:Reference Values; D006435:Renal Dialysis
D001609:Beta-Globulins; D015415:Biomarkers; D054834:Lipocalins; D009844:Oligosaccharides; D011134:Polysaccharides; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase; D019158:N-Acetylneuraminic Acid