Fumonisin B1 inhibits mitochondrial respiration and deregulates calcium homeostasis-Implication to mechanism of cell toxicity
Fumonisin B1 inhibits mitochondrial respiration and deregulates calcium homeostasis-Implication to mechanism of cell toxicity
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DOI：
10.1016/j.biocel.2011.03.003
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发表时间：
2011-06-01
影响因子：
4
通讯作者：
Abramov, Andrey Y.
中科院分区：
文献类型：
--
作者：
Domijan, Ana-Marija;Abramov, Andrey Y.
伏马菌素B-1(Fumonisin B-1，FB1)是由玉米枯萎病菌产生的一种神经退行性真菌毒素，污染世界各地的玉米。FB1的毒性与鞘磷脂代谢的紊乱有关，但其细胞毒性的机制仍存在争议。在原代培养的大鼠星形胶质细胞和人神经母细胞瘤(SH-SY5Y)的细胞培养中，我们发现FB1抑制线粒体复合体I，导致线粒体和细胞呼吸速率降低，线粒体膜去极化，诱导线粒体产生活性氧(ROS)，并解除钙信号调节。尽管ROS生成增加，但细胞内谷胱甘肽(GSH)水平显著增加。FB1作用24小时后，未见细胞死亡。因此，线粒体似乎是FB1的主要靶点，它导致钙稳态的持续破坏，并可能导致细胞死亡。(C)2011爱思唯尔有限公司。保留所有权利。
Fumonisin B-1 (FB1) is a neurodegenerative mycotoxin produced by Fusarium verticiloides mould that contaminates maize worldwide. FB1 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 FB1 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 FB1 exposure, no cell death was observed. Thus, mitochondria appear to be the primary target of FB1, which leads to sustained deregulation of calcium homeostasis and presumably to cell death. (C) 2011 Elsevier Ltd. All rights reserved.