Faculty of Chemical Sciences, University of Concepción, Casilla 160C, Concepción, Chile.
Biochem Biophys Res Commun. 2010 Jun 25;397(2):226-31. doi: 10.1016/j.bbrc.2010.05.089. Epub 2010 May 24.
Gold compounds are well known for their neurological and nephrotoxic implications. However, haematological toxicity is one of the most serious toxic and less studied effects. The lack of information on these aspects of Au(III) prompted us to study the structural effects induced on cell membranes, particularly that of human erythrocytes. AuCl(3) was incubated with intact erythrocytes, isolated unsealed human erythrocyte membranes (IUM) and molecular models of the erythrocyte membrane. The latter consisted of multibilayers of dimyristoylphosphatidylcholine and dimyristoylphosphatidylethanolamine, phospholipids classes located in the outer and inner monolayers of the human erythrocyte membrane, respectively. This report presents evidence that Au(III) interacts with red cell membranes as follows: (a) in scanning electron microscopy studies on human erythrocytes it was observed that Au(III) induced shape changes at a concentration as low as 0.01 microM; (b) in isolated unsealed human erythrocyte membranes Au(III) induced a decrease in the molecular dynamics and/or water content at the glycerol backbone level of the lipid bilayer polar groups in a 5-50 microM concentration range, and (c) X-ray diffraction studies showed that Au(III) in the 10 microm-1mM range induced increasing structural perturbation only to dimyristoylphosphatidylcholine bilayers. Additional experiments were performed in human neuroblastoma cells SH-SY5Y. A statistically significant decrease of cell viability was observed with Au(III) ranging from 0.1 microM to 100 microM.
金化合物以其对神经系统和肾脏的毒性而闻名。然而,血液毒性是最严重的毒性之一,也是研究较少的毒性之一。由于缺乏有关金(III)这些方面的信息,我们研究了其对细胞膜的结构影响,特别是对人红细胞的影响。将 AuCl3 与完整的红细胞、分离的未密封人红细胞膜(IUM)和红细胞膜的分子模型孵育。后者由二肉豆蔻酰磷脂酰胆碱和二肉豆蔻酰磷脂酰乙醇胺的多层组成,磷脂类分别位于人红细胞膜的外层和内层单层中。本报告提供了以下证据表明 Au(III)与人红细胞膜相互作用:(a)在对人红细胞的扫描电子显微镜研究中观察到,Au(III)在低至 0.01 microM 的浓度下即可诱导形状变化;(b)在分离的未密封的人红细胞膜中,Au(III)在 5-50 microM 浓度范围内诱导脂质双层极性基团甘油骨架水平的分子动力学和/或水含量降低,(c)X 射线衍射研究表明,Au(III)在 10 µm-1 mM 范围内仅诱导二肉豆蔻酰磷脂酰胆碱双层的结构扰动增加。在人神经母细胞瘤细胞 SH-SY5Y 中进行了额外的实验。观察到 Au(III)从 0.1 microM 到 100 microM 范围使细胞活力显著下降。