Naslov
Mitochondrial dysfunction in fumonisin B1 neurotoxicity

Autori
Domijan, Ana-Marija

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Power of Fungi and Mycotoxins in Health and Disease, Programme and Abstracts / Antolović, Roberto ; Miličević, Tihomir - Zagreb : Hrvatsko mikrobiološko društvo, 2011, 32-32

ISBN
978-953-7778-01-9

Skup
Power of Fungi and Mycotoxins in Health and Disease

Mjesto i datum
Primošten, Hrvatska, 19.10.2011. - 21.10.2011

Vrsta sudjelovanja
Pozvano predavanje

Vrsta recenzije
Domaća recenzija

Ključne riječi
astrocytes; neuroblastoma cells; reactive oxygen species; calcium homeostasis

Sažetak
Fumonisin B1 (FB1) is a mycotoxin, produced by Fusarium verticiloides mould, a common fungal contaminant of maize world-wide. Its toxicity is well established in domestic and experimental animals. In regions of South Africa and Central America where maize is staple food, human exposure to FB1 is linked with higher incidence of neural tube defect. Although FB1 toxicity has been connected with deregulation of sphingolipid metabolism, the mechanism of its induction of cell death still remains unclear. To investigate the cellular mechanism of FB1 neurotoxicity, a series of experiments on cell cultures of rat primary astrocytes and human neuroblastoma cells (SH-SY5Y) were performed. The cells were treated with FB1 (0.5 µM, 5 µM and 50 µM), concentrations that humans possibly can be exposed to, and changes in cytosolic calcium level, mitochondrial depolarization, reactive oxygen species (ROS) production and GSH level were monitored. The “live imaging” on epifluorescent inverted microscope of cytosolic calcium level was followed with fura-2 AM, changes in mitochondrial membrane potential with Rhodamine 123, cytosolic ROS production with dihydroethidium, ROS production in mitochondria with MitoSOX, and GSH level with monochlorobiamine. To further explore the impact of FB1 on the respiration rate in intact cells and on the mitochondrial respiration a Clark-type oxygen electrode was used. The obtained results showed that FB1 inhibits mitochondrial complex I of the respiratory chain, which leads to a decrease in the rate of mitochondrial and cellular respiration, depolarisation of the mitochondrial membrane, induction of ROS production in mitochondria and deregulation of calcium signalling. Despite the increase in ROS production, the intracellular level of GSH was significantly increased. Thus, mitochondria appear to be the primary target of FB1, which leads to sustained deregulation of calcium homeostasis and presumably to cell death.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

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