Wei S, Gamble M V, Vogel S, Piantedosi R, Gottesman M, Episkopou V, Blaner W S
Institute of Human Nutrition, the Department of Medicine, and the Institute of Cancer Research of the College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
J Biol Chem. 2001 Jan 12;276(2):1107-13. doi: 10.1074/jbc.M008091200.
Transthyretin (TTR) acts physiologically in the transport of retinol in the circulation. We previously reported the generation and partial characterization of TTR-deficient (TTR(-)) mice. TTR(-) mice have very low circulating levels of retinol and its specific transport protein, retinol-binding protein (RBP). We have examined the biochemical basis for the low plasma retinol-RBP levels. Cultured primary hepatocytes isolated from wild type (WT) and TTR(-) mice accumulated RBP in their media to an identical degree, suggesting that RBP was being secreted from the hepatocytes at the same rate. In vivo experiments support this conclusion. For the first 11 h after complete nephrectomy, the levels retinol and RBP rose in the circulations of WT and TTR(-) mice at nearly identical rates. However, human retinol-RBP injected intravenously was more rapidly cleared from the circulation (t(12) = 0.5 h for TTR(-) versus t(12) >6 h for WT) and accumulated faster in the kidneys of TTR(-) compared with WT mice. The rate of infiltration of the retinol-RBP complex from the circulation to tissue interstitial fluids was identical in both strains. Taken together, these data indicate that low circulating retinol-RBP levels in TTR(-) mice arise from increased renal filtration of the retinol-RBP complex.
甲状腺素转运蛋白（TTR）在循环中参与视黄醇的转运，发挥生理作用。我们之前报道了TTR基因缺陷（TTR(-)）小鼠的产生及部分特征。TTR(-)小鼠循环中的视黄醇及其特异性转运蛋白视黄醇结合蛋白（RBP）水平极低。我们研究了血浆视黄醇-RBP水平降低的生化基础。从野生型（WT）和TTR(-)小鼠分离培养的原代肝细胞，在其培养基中积累RBP的程度相同，这表明RBP从肝细胞分泌的速率相同。体内实验支持这一结论。在全肾切除后的前11小时，WT和TTR(-)小鼠循环中的视黄醇和RBP水平以几乎相同的速率上升。然而，静脉注射的人视黄醇-RBP从循环中清除的速度更快（TTR(-)小鼠的t(12)=0.5小时，而WT小鼠的t(12)>6小时），并且与WT小鼠相比，TTR(-)小鼠的肾脏中视黄醇-RBP积累得更快。视黄醇-RBP复合物从循环渗入组织间质液的速率在两种品系中相同。综上所述，这些数据表明TTR(-)小鼠循环中视黄醇-RBP水平较低是由于视黄醇-RBP复合物的肾脏滤过增加所致。
