Department of Bioscience and Biotechnology, Dalian University of Technology, No. 2 Linggong Road, Ganjingzi District, Dalian 116024, China.
Environ Toxicol Pharmacol. 2009 Jan;27(1):103-10. doi: 10.1016/j.etap.2008.08.010. Epub 2008 Sep 7.
Methylmercury (MeHg), as a well-known neurotoxicant, has been implicated to induce massive neurodegeneration. Pyrroloquinoline quinone (PQQ) is a novel redox cofactor and also exists in various plants and animal tissues. In vivo as well as in vitro experimental studies have shown that PQQ functions as an essential nutrient or antioxidant. In this study, we demonstrated the protective effects of PQQ on MeHg-induced neurotoxicity in PC12 cells. The results showed that after pretreatment of PC12 cells with PQQ prior to MeHg exposure, the MeHg-induced cytotoxicity was significantly attenuated, and then DNA fragmentation was correspondingly reduced. PQQ prevented the disruption of mitochondrial membrane potential, up-regulated the level of Bcl-2, and consequently inhibited the activation of caspase-3. Moreover, PQQ also decreased the production of ROS and maintained the GSH levels in PC12 cells exposed to MeHg. Thus, these data indicate that PQQ can protect neurons against MeHg-induced apoptosis and oxidative stress via ameliorating the mitochondrial dysfunction. Data from this study provide a new useful strategy for the treatment of neuronal toxicity induced by mercury toxins.
甲基汞(MeHg)作为一种众所周知的神经毒素,已被证实可诱导大量神经退行性病变。吡咯喹啉醌(PQQ)是一种新型氧化还原辅因子,存在于各种植物和动物组织中。体内和体外实验研究表明,PQQ 作为一种必需营养物质或抗氧化剂发挥作用。在这项研究中,我们证明了 PQQ 对 MeHg 诱导的 PC12 细胞神经毒性的保护作用。结果表明,MeHg 暴露前用 PQQ 预处理 PC12 细胞后,MeHg 诱导的细胞毒性明显减弱,随后 DNA 片段化相应减少。PQQ 防止了线粒体膜电位的破坏,上调了 Bcl-2 的水平,从而抑制了 caspase-3 的激活。此外,PQQ 还减少了 MeHg 暴露的 PC12 细胞中 ROS 的产生并维持 GSH 水平。因此,这些数据表明,PQQ 通过改善线粒体功能障碍,可以保护神经元免受 MeHg 诱导的细胞凋亡和氧化应激。本研究的数据为治疗汞毒素诱导的神经元毒性提供了一种新的有用策略。