The effect of Pb2+ on the structure and hydroxyapatite binding properties of osteocalcin
The effect of Pb2+ on the structure and hydroxyapatite binding properties of osteocalcin
复制标题
DOI：
10.1016/s0925-4439(00)00094-6
复制
发表时间：
2001-02-14
影响因子：
6.2
通讯作者：
Gundberg, CM
中科院分区：
文献类型：
--
作者：
Dowd, TL;Rosen, JF;Gundberg, CM
铅中毒是美国一个主要的环境健康问题。骨骼是体内铅的主要储存库。虽然铅已被证明在动物和细胞水平上损害骨代谢，但Pb2+在分子水平上的影响在很大程度上是未知的。我们使用了圆二色性（CD）和羟基磷灰石结合实验来研究Pb2+对骨钙素（一种非胶原骨蛋白）结构和矿物结合特性的影响。CD数据表明，Pb2+诱导骨钙素的结构与Ca2+相似，但浓度低2个数量级。这些结果可以解释为Pb2+与骨钙素（K-d = 0.085 mM）的结合比Ca2+ (K-d = 125 mM)紧密4个数量级以上。羟基磷灰石结合实验表明，Pb2+引起羟基磷灰石的吸附增加，类似于Ca2+，但浓度低2-3个数量级。低Pb2+水平（1 muM）和生理Ca2+水平（1 mM）导致矿物质结合骨钙素的量与单独1 mM Ca2+相比显著（40%）增加。这些结果提示了Pb2+毒性的分子机制，其中低Pb2+水平可以不适当地干扰Ca2+调节过程。在体内，矿物质结合骨钙素的增加可能与Pb2+中毒动物的低骨形成率和骨密度降低有关。(C) 2001 Elsevier Science B.V.版权所有
Lead toxicity is a major environmental health problem in the United States. Bone is the major reservoir for body lead. Although lead has been shown to impair bone metabolism in animals and at the cellular level, the effect of Pb2+ at the molecular level is largely unknown. We have used circular dichroism (CD), and a hydroxyapatite binding assay to investigate the effect of Pb2+ on the structure and mineral binding properties of osteocalcin, a noncollagenous bone protein. The CD data indicate Pb2+ induces a similar structure in osteocalcin as Ca2+ but at 2 orders of magnitude lower concentration. These results were explained by the more than 4 orders of magnitude tighter binding of Pb2+ to osteocalcin (K-d = 0.085 muM) than Ca2+ (K-d = 1 25 mM). The hydroxyapatite binding assays show that Pb2+ causes an increased adsorption to hydroxyapatite, similar to Ca2+, but at 2-3 orders of magnitude lower concentration. Low Pb2+ levels (1 muM) in addition to physiological Ca2+ levels (1 mM) caused a significant (40%) increase in the amount of mineral bound osteocalcin as compared to 1 mM Ca2+ alone. These results suggest a molecular mechanism of Pb2+ toxicity where low Pb2+ levels can inappropriately perturb Ca2+ regulated processes. In-vivo, the increased mineral bound osteocalcin could play a role in the observed low bone formation rates and decreased bone density observed in Pb2+-intoxicated animals. (C) 2001 Elsevier Science B.V. All rights reserved.