Nanosize titanium dioxide stimulates reactive oxygen species in brain microglia and damages neurons in vitro.
Nanosize titanium dioxide stimulates reactive oxygen species in brain microglia and damages neurons in vitro.
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DOI：
10.1289/ehp.10216
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发表时间：
2007-11
影响因子：
10.4
通讯作者：
Veronesi B
中科院分区：
文献类型：
--
作者：
Long TC;Tajuba J;Sama P;Saleh N;Swartz C;Parker J;Hester S;Lowry GV;Veronesi B
二氧化钛是一种广泛使用的纳米材料，其光反应性表明其可能损害生物靶（例如，氧化应激（oxidative stress，OS）。将永生化小鼠小胶质细胞（BV2）、大鼠多巴胺能（DA）神经元（N27）的脑培养物和胚胎大鼠纹状体的原代培养物暴露于Degussa P25（一种市售TiO 2纳米材料）。P25的物理性质是在生物学测量的条件下测量的。P25在生理缓冲液（800 - 1，900 nm; 25 ° C）和暴露介质（~330 nm; 37 ° C）中快速聚集，并在缓冲液（-12.2 ± 1.6 mV）和介质（-9.1 ± 1.2 mV）中保持负ζ电位。暴露于P25（2.5 - 120 ppm）的BV2小胶质细胞响应于活性氧（ROS）的立即和延长的释放。暴露24小时（≥ 100 ppm）和48小时（≥ 2.5 ppm）后，Hoechst核染色减少。P25暴露的BV2小胶质细胞的微阵列分析表明炎症，凋亡和细胞周期途径的上调和能量代谢的下调。P25（2.5 - 120 ppm）刺激分离的N27神经元（24 - 48小时）细胞内ATP和caspase 3/7活性的增加，但在暴露72小时后不产生细胞毒性。暴露于P25（5 ppm）的大鼠纹状体的原代培养物显示，6小时暴露后，化学染色的神经元和神经元凋亡的显微镜证据减少。这些发现表明P25刺激BV2小胶质细胞中的ROS，并且对分离的N27神经元无毒。然而，在复杂的脑培养物中，P25在低浓度下迅速损伤神经元，尽管小胶质细胞产生ROS。
Titanium dioxide is a widely used nanomaterial whose photo-reactivity suggests that it could damage biological targets (e.g., brain) through oxidative stress (OS). Brain cultures of immortalized mouse microglia (BV2), rat dopaminergic (DA) neurons (N27), and primary cultures of embryonic rat striatum, were exposed to Degussa P25, a commercially available TiO2 nanomaterial. Physical properties of P25 were measured under conditions that paralleled biological measures. P25 rapidly aggregated in physiological buffer (800–1,900 nm; 25°C) and exposure media (~ 330 nm; 37°C), and maintained a negative zeta potential in both buffer (–12.2 ± 1.6 mV) and media (–9.1 ± 1.2 mV). BV2 microglia exposed to P25 (2.5–120 ppm) responded with an immediate and prolonged release of reactive oxygen species (ROS). Hoechst nuclear stain was reduced after 24-hr (≥100 ppm) and 48-hr (≥2.5 ppm) exposure. Microarray analysis on P25-exposed BV2 microglia indicated up-regulation of inflammatory, apoptotic, and cell cycling pathways and down-regulation of energy metabolism. P25 (2.5–120 ppm) stimulated increases of intracellular ATP and caspase 3/7 activity in isolated N27 neurons (24–48 hr) but did not produce cytotoxicity after 72-hr exposure. Primary cultures of rat striatum exposed to P25 (5 ppm) showed a reduction of immunohistochemically stained neurons and microscopic evidence of neuronal apoptosis after 6-hr exposure. These findings indicate that P25 stimulates ROS in BV2 microglia and is nontoxic to isolated N27 neurons. However, P25 rapidly damages neurons at low concentrations in complex brain cultures, plausibly though microglial generated ROS.
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影响因子：
22.1
作者：
Choi, H;Stathatos, E;Dionysiou, DD
通讯作者：
Dionysiou, DD
影响因子：
4.5
作者：
Gurr, JR;Wang, ASS;Jan, KY
通讯作者：
Jan, KY
影响因子：
4.5
作者：
Lockman, PR;Koziara, JM;Allen, DD
通讯作者：
Allen, DD
影响因子：
6.2
作者：
Husemann, J;Loike, JD;Silverstein, SC
通讯作者：
Silverstein, SC
影响因子：
4.8
作者：
Block, ML;Wu, X;Veronesi, B
通讯作者：
Veronesi, B