Breen K C, Regan C M
Dept. of Pharmacology, University College, Dublin, Ireland.
Toxicology. 1988 Apr;49(1):71-6. doi: 10.1016/0300-483x(88)90176-x.
The neural cell adhesion molecule N-CAM is believed to be intimately involved in the structuring of the central nervous system. During post-natal development the molecule exists in 2 forms--a sialic acid-rich form which is preferentially expressed during cell acquisition and fibre outgrowth and a sialic acid-poor form which appears at times coincident with synaptogenesis. The developmental changes between these 2 forms have been demonstrated to be impaired by chronic low-level lead exposure and this is consistent with the reduced synaptic elaboration associated with this action. Here is described the effect of lead on the Golgi-associated sialyltransferase which regulates N-CAM sialylation state. Lead chloride was found to markedly stimulate sialyltransferase with an ED50 of 5 X 10(-7) M in adult Golgi fractions. This was not observed in fractions derived from 12-day old animals. At the concentration of 5 X 10(-5) M lead was found to have a differential effect on the developmental expression of this enzyme. During the early phases of development (days 4-16) sialyltransferase activity was inhibited. However, in coincidence with periods of N-CAM desialylation (days 16-30), it was significantly stimulated. These findings are related to the perturbations of N-CAM function during chronic low-level lead exposure.
神经细胞黏附分子N-CAM被认为与中枢神经系统的结构密切相关。在出生后的发育过程中,该分子以两种形式存在——一种富含唾液酸的形式,在细胞获取和纤维生长过程中优先表达;另一种唾液酸含量低的形式,出现在与突触形成同时的时期。这两种形式之间的发育变化已被证明会因长期低水平铅暴露而受损,这与这种作用相关的突触细化减少是一致的。本文描述了铅对调节N-CAM唾液酸化状态的高尔基体相关唾液酸转移酶的影响。在成年高尔基体组分中,发现氯化铅能显著刺激唾液酸转移酶,其半数有效剂量(ED50)为5×10^(-7) M。在来自12日龄动物的组分中未观察到这种情况。在5×10^(-5) M的浓度下,发现铅对这种酶的发育表达有不同的影响。在发育的早期阶段(第4 - 16天),唾液酸转移酶活性受到抑制。然而,与N-CAM去唾液酸化时期(第16 - 30天)一致,它受到显著刺激。这些发现与长期低水平铅暴露期间N-CAM功能的扰动有关。