Faculty of Environmental Science and Engineering, Kunming University of Science and Technology, Kunming 650500, China.
Neurotoxicology. 2012 Jun;33(3):290-8. doi: 10.1016/j.neuro.2012.02.004. Epub 2012 Feb 10.
Formaldehyde (FA), a common environmental pollutant, has toxic effects on central nervous system. The detailed mechanisms on FA-induced neurotoxicity have not been fully elucidated. In this study, we found that glucose regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP) expression, biomarkers of endoplasmic reticulum (ER) stress, were increased and pro-caspase-12 was decreased after PC12 cells exposure to FA. These results suggest that FA actually induces ER stress. Thioredoxin-1 (Trx-1) has various biological activities, including the control of redox balance, the modulation of ER stress and inhibition of apoptosis. In the present study, Trx-1 expression was increased at early stage, but decreased at late stage after FA treatment. Knockdown of Trx-1 expression increased the susceptibility of PC12 cells to FA-induced neurotoxicity. We also found that ginsenoside Rg1 had the potential to induce Trx-1 expression and attenuated neurotoxicity induced by FA. ER stress caused by FA was suppressed by ginsenoside Rg1. These data indicate that Trx-1 is a therapeutic candidate for protecting against FA-induced neurotoxicity.
甲醛（FA）是一种常见的环境污染物，对中枢神经系统有毒性作用。FA 诱导神经毒性的详细机制尚未完全阐明。在这项研究中，我们发现 PC12 细胞暴露于 FA 后，内质网（ER）应激的生物标志物葡萄糖调节蛋白 78（GRP78）和 C/EBP 同源蛋白（CHOP）的表达增加，前半胱氨酸天冬氨酸蛋白酶-12（pro-caspase-12）减少。这些结果表明 FA 实际上会诱导 ER 应激。硫氧还蛋白-1（Trx-1）具有多种生物学活性，包括控制氧化还原平衡、调节 ER 应激和抑制细胞凋亡。在本研究中，FA 处理后早期 Trx-1 表达增加，但晚期表达减少。Trx-1 表达下调会增加 PC12 细胞对 FA 诱导的神经毒性的易感性。我们还发现，人参皂苷 Rg1 具有诱导 Trx-1 表达和减轻 FA 诱导的神经毒性的潜力。人参皂苷 Rg1 抑制了 FA 引起的 ER 应激。这些数据表明，Trx-1 是一种治疗 FA 诱导神经毒性的候选药物。
