Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.
Int J Biochem Cell Biol. 2011 Jun;43(6):897-904. doi: 10.1016/j.biocel.2011.03.003. Epub 2011 Mar 10.
Fumonisin B(1) (FB(1)) is a neurodegenerative mycotoxin produced by Fusarium verticiloides mould that contaminates maize worldwide. FB(1) toxicity has been connected with deregulation of sphingolipid metabolism, but the mechanism of cytotoxicity remains controversial. In cell cultures of rat primary astrocytes and human neuroblastoma (SH-SY5Y), we found that FB(1) inhibits mitochondrial complex I, which leads to a decrease in the rate of mitochondrial and cellular respiration, depolarisation of the mitochondrial membrane, induction of reactive oxygen species (ROS) production in mitochondria and deregulation of calcium signalling. Despite the increase in ROS production, the intracellular level of glutathione (GSH) was significantly increased. After 24h of FB(1) exposure, no cell death was observed. Thus, mitochondria appear to be the primary target of FB(1), which leads to sustained deregulation of calcium homeostasis and presumably to cell death.
伏马菌素 B(1)（FB(1)）是一种由串珠镰刀菌产生的神经退行性霉菌毒素，它污染了世界各地的玉米。FB(1)的毒性与鞘脂代谢失调有关，但细胞毒性的机制仍存在争议。在大鼠原代星形胶质细胞和人神经母细胞瘤（SH-SY5Y）的细胞培养物中，我们发现 FB(1)抑制线粒体复合物 I，导致线粒体和细胞呼吸率下降，线粒体膜去极化，诱导线粒体中活性氧（ROS）的产生，并导致钙信号失调。尽管 ROS 的产生增加，但细胞内谷胱甘肽 (GSH) 的水平显著增加。FB(1)暴露 24 小时后，未观察到细胞死亡。因此，线粒体似乎是 FB(1)的主要靶标，这导致钙稳态的持续失调，可能导致细胞死亡。
