Takata K, Horiuchi S, Araki N, Shiga M, Saitoh M, Morino Y
Department of Biochemistry, Kumamoto University Medical School, Japan.
J Biol Chem. 1988 Oct 15;263(29):14819-25.
Long term incubation of proteins with glucose, named the Maillard reaction (Maillard, L. C. (1912) C. R. Acad. Sci. (Paris) 154, 66-68), gives rise to advanced glycosylation end product (AGE) with fluorescence, color, as well as cross-linked properties. The receptor-mediated endocytosis of AGE-proteins by macrophages was reported (Vlassara, H., Brownlee, M., and Cerami, A. (1985) Proc. Natl. Acad. Sci. U.S.A. 82, 5588-5592). The present study on the binding of AGE-bovine serum albumin (BSA) to rat peritoneal macrophages and sinusoidal liver cells demonstrated the presence of a saturable, high affinity receptor for AGE-BSA with Kd = 2.4 x 10(-7) M (macrophages) and 2.1 x 10(-7) M (sinusoidal cells). The cellular binding of AGE-BSA and its endocytic uptake by these cells were competitively inhibited by BSA preparations modified with aliphatic aldehydes such as formaldehyde or glycolaldehyde, ligands known to be specific for a scavenger receptor for aldehyde-modified proteins (Horiuchi, S., Murakami, M., Takata, K., and Morino, Y. (1986). J. Biol. Chem. 261, 4962-4966). These ligands also had a profound in vivo effect on the plasma clearance of 125I-AGE-BSA as well as its hepatic uptake. Thus, endocytic uptake of AGE-proteins by macrophages appeared to be mediated by a scavenger receptor for aldehyde-modified proteins. This provides evidence for the biological importance of the scavenger receptor in eliminating senescent macromolecules from the circulation.
蛋白质与葡萄糖的长期孵育，即所谓的美拉德反应（美拉德，L.C.（1912年）《法国科学院院报》（巴黎）154卷，66 - 68页），会产生具有荧光、颜色以及交联特性的晚期糖基化终产物（AGE）。据报道，巨噬细胞可通过受体介导的内吞作用摄取AGE - 蛋白质（弗拉萨拉，H.，布朗利，M.，和塞拉米，A.（1985年）《美国国家科学院院刊》82卷，5588 - 5592页）。本研究关于AGE - 牛血清白蛋白（BSA）与大鼠腹膜巨噬细胞和肝血窦细胞的结合，证明存在一种对AGE - BSA具有饱和性、高亲和力的受体，其解离常数Kd = 2.4×10⁻⁷M（巨噬细胞）和2.1×10⁻⁷M（肝血窦细胞）。AGE - BSA与这些细胞的细胞结合及其内吞摄取受到用脂肪醛如甲醛或乙醇醛修饰的BSA制剂的竞争性抑制，这些配体已知是醛修饰蛋白质清道夫受体的特异性配体（堀内，S.，村上，M.，高田，K.，和森野，Y.（1986年）《生物化学杂志》261卷，4962 - 4966页）。这些配体对¹²⁵I - AGE - BSA的血浆清除率及其肝脏摄取也有显著的体内效应。因此，巨噬细胞对AGE - 蛋白质的内吞摄取似乎是由醛修饰蛋白质的清道夫受体介导的。这为清道夫受体在从循环中清除衰老大分子方面的生物学重要性提供了证据。
