The interaction of manganese nanoparticles with PC-12 cells induces dopamine depletion
The interaction of manganese nanoparticles with PC-12 cells induces dopamine depletion
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DOI：
10.1093/toxsci/kfl020
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发表时间：
2006-08-01
影响因子：
3.8
通讯作者：
Schlager, John J.
中科院分区：
文献类型：
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作者：
Hussain, Saber M.;Javorina, Amanda K.;Schlager, John J.
本研究旨在确定纳米氧化锰 (Mn-40nm) 颗粒是否会在培养的神经元表型 PC-12 细胞中诱导多巴胺 (DA) 消耗，类似于游离离子锰 (Mn2+)。将细胞暴露于 Mn-40nm、Mn2+（醋酸盐）或已知的细胞毒性银纳米颗粒 (Ag-15nm) 中 24 小时。相差显微镜研究表明，Mn-40nm 或 Mn2+ 暴露并未显着改变 PC-12 细胞的形态。然而，与对照细胞相比，Ag-15nm 和 AgNO3 会产生细胞收缩和不规则的膜边界。更高分辨率的进一步显微研究表明，Mn-40nm 纳米粒子和团聚物被 PC-12 细胞有效内化。线粒体还原活性是颗粒和金属细胞毒性的敏感指标，与类似的 Ag-15nm 和 Mn2+ 剂量相比，Mn-40nm 仅表现出中等毒性。 Mn-40nm和Mn2+剂量依赖性地消耗DA及其代谢物二羟基苯乙酸(DOPAC)和高香草酸(HVA)，而Ag-15nm仅在浓度为50μg/ml时显着减少DA和DOPAC。因此，Mn-40nm 的 DA 消耗与 Mn2+ 最相似，Mn2+ 已知会诱导浓度依赖性 DA 消耗。 Mn-40nm 暴露后，活性氧 (ROS) 显着增加（> 10 倍），表明 ROS 水平增加可能参与 DA 消耗。这些结果清楚地表明，纳米级锰可以以剂量依赖性方式消耗 DA、DOPAC 和 HVA。需要进一步的研究来评估 Mn-40nm 纳米粒子的特定细胞内分布、细胞和细胞基质中的金属溶解率、体内诱导 DA 消耗的情况，以及 Mn 纳米粒子穿过血脑屏障或被鼻上皮选择性摄取的倾向。
This investigation was designed to determine whether nano-sized manganese oxide (Mn-40nm) particles would induce dopamine (DA) depletion in a cultured neuronal phenotype, PC-12 cells, similar to free ionic manganese (Mn2+). Cells were exposed to Mn-40nm, Mn2+ (acetate), or known cytotoxic silver nanoparticles (Ag-15nm) for 24 h. Phase-contrast microscopy studies show that Mn-40nm or Mn2+ exposure did not greatly change morphology of PC-12 cells. However, Ag-15nm and AgNO3 produce cell shrinkage and irregular membrane borders compared to control cells. Further microscopic studies at higher resolution demonstrated that Mn-40nm nanoparticles and agglomerates were effectively internalized by PC-12 cells. Mitochondrial reduction activity, a sensitive measure of particle and metal cytotoxicity, showed only moderate toxicity for Mn-40nm compared to similar Ag-15nm and Mn2+ doses. Mn-40nm and Mn2+ dose dependently depleted DA and its metabolites, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), while Ag-15nm only significantly reduced DA and DOPAC at concentrations of 50 mu g/ml. Therefore, the DA depletion of Mn-40nm was most similar to Mn2+, which is known to induce concentration-dependent DA depletion. There was a significant increase (> 10-fold) in reactive oxygen species (ROS) with Mn-40nm exposure, suggesting that increased ROS levels may participate in DA depletion. These results clearly demonstrate that nanoscale manganese can deplete DA, DOPAC, and HVA in a dose-dependent manner. Further study is required to evaluate the specific intracellular distribution of Mn-40nm nanoparticles, metal dissolution rates in cells and cellular matrices, if DA depletion is induced in vivo, and the propensity of Mn nanoparticles to cross the blood-brain barrier or be selectively uptaken by nasal epithelium.