Characterization of two post-translationally processed forms of human serum retinol-binding protein: altered ratios in chronic renal failure.
Retinol-binding protein (RBP) is the specific blood carrier for the transport of retinol (vitamin A) to target tissues. As the kidney is involved in RBP metabolism, the analysis of RBP species in the serum of patients with chronic renal failure (CRF) was used as a model to study possible RBP alterations. SDS-PAGE-immunoblotting analysis of normal and CRF sera shows a doublet of RBP bands (band A and band B) near 21 kDa. Mass spectrometric analysis of purified RBPs from CRF and normal sera revealed the presence not only of full-length RBP (183 residues, migrating in band A) but also two forms of RBP differing from the native form by the loss of C-terminal Leu (i.e., RBP1 (residues 1-182), migrating in band A also) and the loss of C-terminal Leu-Leu (i.e., RBP2 (residues 1-181), migrating in band B). Interestingly, RBP2 was considerably increased in the serum of CRF, whereas it was low in normal sera. In healthy retinol target-tissues and in cultured HepG2 cells, RBP2 levels were significantly and variably present compared to RBP and RBP1. We propose that these post-translationally modified forms of RBP occur in cells and that after their release into the blood circulation RBP2 is cleared by the kidney in healthy individuals but accumulates in the serum of CRF patients. RBP2 may have an important physiological role in retinol transport and/or recycling.
Jaconi
S
S
Clinique de Dermatologie, Hôpital Cantonal Universitaire, Genève, Switzerland.
Rose
K
K
Hughes
G J
GJ
Saurat
J H
JH
Siegenthaler
G
G
D000595:Amino Acid Sequence; D002268:Carboxypeptidases / Q000378:metabolism; D043422:Carboxypeptidases A; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D015151:Immunoblotting; D007676:Kidney Failure, Chronic / Q000097:blood*; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D011228:Prealbumin / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D012177:Retinol-Binding Proteins / Q000378:metabolism*
D011228:Prealbumin; D012177:Retinol-Binding Proteins; D002268:Carboxypeptidases; D043422:Carboxypeptidases A