Binding of a metabolite of 3,4,3',4'-tetrachlorobiphenyl to transthyretin reduces serum vitamin A transport by inhibiting the formation of the protein complex carrying both retinol and thyroxin.
The mechanism of serum vitamin A reduction by polychlorinated biphenyls was studied at the level of the plasma transport protein system for vitamin A. Analysis of [3H]retinol-labeled serum proteins by polyacrylamide gel electrophoresis (PAGE) showed association of retinol with two proteins that were identified as retinol binding protein (RBP) and the RBP complex with transthyretin (TTR). The amount of [3H]retinol radioactivity in the serum as well as the label associated with the binding proteins was strongly reduced by 3,4,3',4'-tetrachlorobiphenyl (TCB). A possible interaction of TCB with the retinol binding proteins was investigated, using radiolabeled TCB. Analysis of the plasma proteins by PAGE revealed the presence of four peaks of 3H-TCB label, the major ones being associated with lipoproteins and TTR. No 3H-TCB radioactivity was found in the region of the gel where RBP or the RBP-TTR complex was located. HPLC analysis of the radioactive compound associated with TTR showed the presence of a metabolite of TCB, rather than the parent compound. These data indicate a direct interaction of a metabolite of TCB with TTR leading to an inhibition of formation of the serum transport protein complex carrying both retinol and thyroxin. A model is proposed, which may explain certain characteristic toxicopathological lesions observed in species exposed to polychlorinated biphenyls and related compounds (TCDD, PBBs, etc.).
D000818:Animals; D001667:Binding, Competitive; D001692:Biological Transport; D005260:Female; D011078:Polychlorinated Biphenyls / Q000378:metabolism*; D011228:Prealbumin / Q000378:metabolism*; D051381:Rats; D012177:Retinol-Binding Proteins / Q000378:metabolism; D054839:Retinol-Binding Proteins, Plasma; D013974:Thyroxine / Q000378:metabolism*; D014801:Vitamin A / Q000097:blood*
D011228:Prealbumin; D012177:Retinol-Binding Proteins; D054839:Retinol-Binding Proteins, Plasma; D014801:Vitamin A; D011078:Polychlorinated Biphenyls; D013974:Thyroxine; C028451:3,4,3',4'-tetrachlorobiphenyl