engleski

Deregulation of calcium signalling in fumonisin B1 neurotoxicity

Fumonisin B1 (FB1) is a neurotoxic mycotoxin that contaminates maize and maize-based food all around the world. Molecular mechanism underlying FB1 toxicity as well as neurotoxicity is still not known. On the cells of neuronal origin we explored effect of FB1 on calcium signalling and mitochondrial membrane potential. In our study FB1 (0.5, 5 and 50 μM) in astrocytes and neuroblastoma cells was able to significantly increase calcium signal compared to control cells and produce mitochondrial membrane depolarisation in concentration-dependent manner. These results indicate that FB1 primarily targets mitochondria causing depolarisation of mitochondrial membrane that leads to calcium deregulation and presumably to cell death. To confirm this finding we checked possible impact of FB1 on physiological and pathological conditions in the brain that are characterised with calcium deregulation and mitochondrial membrane depolarisation. In all three tested models, the low glutamate model, the glutamate excitotoxicity model, and the low magnesium model of epilepsy, pre-treatment of hippocampal neurones with FB1 (0.5 and 10 μM) increased or changed cytosolic calcium level simultaneously with mitochondrial membrane depolarisation. Since FB1 alone induced mitochondrial depolarisation and limited mitochondrial ability to uptake calcium, the higher calcium signal in neurons after pre-treatment with FB1 in tested models can be explained by lower calcium uptake in mitochondria. Taken together our results indicate that FB1, even in very low concentrations that humans can be exposed to, deregulates calcium signalling and can act as a trigger to cell death.

fumonisin B1; neurotoxicity; calcium signalling

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