Pak Eun Joo, Son Gi Dong, Yoo Byung Sun
Department of Life Science, Kyonggi University, Suwon, Republic of Korea.
Department of Life Science, Kyonggi University, Suwon, Republic of Korea
Int J Toxicol. 2014 Sep-Oct;33(5):412-8. doi: 10.1177/1091581814550338. Epub 2014 Sep 22.
Cadmium, a highly ubiquitous heavy metal, is well known to induce neurotoxicity. However, the underlying mechanism of cadmium-mediated neurotoxicity remains unclear. We have studied cadmium inhibition of neurite outgrowth using human SH-SY5Y neuroblastoma cells induced to differentiate by all-trans-retinoic acid (RA). Cadmium, at a concentration of 3 μmol/L, had no significant effect on the viability of differentiating SH-SY5Y cells. However, the neurite outgrowth of the differentiating SH-SY5Y cells 48 hours after cadmium treatment (1-3 μmol/L cadmium) was significantly inhibited in a dose-dependent manner. Treatment of RA-stimulated differentiating SH-SY5Y cells with 1 to 3 μmol/L cadmium resulted in decreased level of cross-reactivities with 43-kDa growth-associated protein (GAP-43) in a dose-dependent manner. The reactive oxygen species (ROS) scavenger, NAC (N-acetyl-l-cysteine), recovered the expression of GAP-43 in cadmium-treated cells. The results indicate that cadmium is able to inhibit neurite outgrowth of differentiating SH-SY5Y cells and that this effect might result from ROS generation by cadmium.
镉是一种广泛存在的重金属，众所周知会诱发神经毒性。然而，镉介导的神经毒性的潜在机制仍不清楚。我们使用经全反式维甲酸（RA）诱导分化的人SH-SY5Y神经母细胞瘤细胞研究了镉对神经突生长的抑制作用。浓度为3μmol/L的镉对分化中的SH-SY5Y细胞的活力没有显著影响。然而，镉处理（1-3μmol/L镉）48小时后，分化中的SH-SY5Y细胞的神经突生长以剂量依赖的方式受到显著抑制。用1至3μmol/L镉处理RA刺激的分化中的SH-SY5Y细胞，导致与43-kDa生长相关蛋白（GAP-43）的交叉反应水平以剂量依赖的方式降低。活性氧（ROS）清除剂N-乙酰半胱氨酸（NAC）恢复了镉处理细胞中GAP-43的表达。结果表明，镉能够抑制分化中的SH-SY5Y细胞的神经突生长，这种作用可能是由镉产生的ROS所致。
