Advanced glycation end products are eliminated by scavenger-receptor-mediated endocytosis in hepatic sinusoidal Kupffer and endothelial cells
Advanced glycation end products are eliminated by scavenger-receptor-mediated endocytosis in hepatic sinusoidal Kupffer and endothelial cells
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DOI：
10.1042/bj3220567
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发表时间：
1997-03-01
影响因子：
4.1
通讯作者：
Horiuchi, S
中科院分区：
文献类型：
--
作者：
Smedsrod, B;Melkko, J;Horiuchi, S
蛋白质与葡萄糖的长期孵育导致晚期糖基化终产物（AGE）的形成。在体内和体外研究了非酶糖化蛋白的催化作用的生理学方面。AGE修饰的BSA（AGE-BSA）是高M（交联）、单体和低M（r）（片段化）AGE-BSA的混合物。大鼠静脉给药后，AGE-BSA的所有三种组分都非常迅速地积累，几乎只在肝脏中积累。肝内皮细胞、枯否细胞和实质细胞的摄取约占肝脏消除率分别为60%、25%和10 - 15%。在纯化的肝内皮细胞和枯否细胞培养物中，交联和单体AGE-BSA均被有效吸收和降解。这些细胞的AGE-BSA的内吞作用被清道夫受体的几种配体抑制。虽然I-125-Hb在体外不被内吞，但I-125-AGE-Hb通过受到AGE-BSA抑制的机制被有效内吞。AGE-Hb和AGE-BSA能有效地抑制清道夫受体的生理配体Ⅰ型前胶原N端前肽的内吞作用。我们的结论是，AGE修饰使得大分子容易通过肝脏内皮细胞和枯否细胞的清道夫受体消除。
Long-term incubation of proteins with glucose leads to the formation of advanced glycation end products (AGE). Physiological aspects of the catabolism of non-enzymically glycated proteins were studied in vivo and in vitro. AGE-modified BSA (AGE-BSA) was a mixture of high-M, (cross-linked), monomeric and low-M(r) (fragmented) AGE-BSA. After intravenous administration in rat, all three fractions of AGE-BSA accumulated extremely rapidly and almost exclusively in liver. Uptake in liver endothelial, Kupffer and parenchymal cells accounted for approx. 60%, 25% and 10-15% respectively of hepatic elimination. Both cross-linked and monomeric AGE-BSA were efficiently taken up and degraded in cultures of purified liver endothelial and Kupffer cells. Endocytosis of AGE-BSA by these cells was inhibited by several ligands for the scavenger receptor. Although I-125-Hb was not endocytosed in vitro, I-125-AGE-Hb was effectively endocytosed by a mechanism that was subject to inhibition by AGE-BSA. Endocytosis of N-terminal propeptide of type I procollagen, a physiological ligand for the scavenger receptor, was effectively inhibited by AGE-Hb and AGE-BSA. We conclude that AGE-modification renders macromolecules susceptible for elimination via the scavenger receptor of both liver endothelial and Kupffer cells.