The ribotoxin deoxynivalenol affects the viability and functions of glial cells

Abstract

Glial cells are responsible for maintaining brain homeostasis. Modification of the viability and functions of glial cells, including astrocytes and microglia, are associated with neuronal death and neurological diseases. Many toxins (heavy metals, pesticides, bacterial or viral toxins) are known to impact on brain cell viability and functions. Although recent publications suggest a potential link between environmental exposure of humans to mycotoxins and neurological diseases, data regarding the effects of fungal toxins on brain cells are scarce. In the present study, we looked at the impact of deoxynivalenol (DON), a fungal ribotoxin, on glial cells from animal and human origin. We found that DON decreased the viability of glial cells with a higher toxicity against microglial cells compared with astrocytes. In addition to cellular toxicity, DON affected key functions of glial cells. Thus, DON caused a biphasic effect on the neuroinflammatory response of microglia to lipopolysaccharide (LPS), while sublethal doses of DON increased the LPS-induced secretion of TNF-α and nitric oxide, toxic doses inhibited it. In addition to affecting microglial functions, sublethal doses of DON also suppressed the uptake of L-glutamate by astrocytes. This inhibition was associated with a modification of the expression of the glutamate transporters at the plasma membrane. Our results suggest that environmental ribotoxins such as DON could, at low doses, cause modifications of brain homeostasis and possibly participate in the etiology of neurological diseases in which alterations of the glia are involved.

Sub-Emetic Toxicity of Bacillus cereus Toxin Cereulide on Cultured Human Enterocyte-Like Caco-2 Cells

“…Triosephosphate isomerase 1 is an enzyme involved in glycolysis. It is downregulated after treatment of hepatic cell lines with certain antimicrobial peptides (a role characteristic of CER, too [40]), resulting in apoptosis [41], and with deoxynivalenol [42], which is an emetic mycotoxin from Fusarium species [43], with known toxicity on gut and brain cells [44]. It has also been demonstrated that neurotoxin-like beta-carbolines, which are inhibitors of mitochondrial respiration, bind to this protein [45].…”

Mislocalization of the exitatory amino-acid transporters (EAATs) in human astrocytoma and non-astrocytoma cancer cells: effect of the cell confluence

“…Flasks were maintained in a humidified incubator at 37°C with 95% air and 5% CO 2 . Primary cultures of cortical astrocytes were prepared from new born rats as previously described [21,22]. …”

“…Concentration of L-glutamate was measured using enzymatic quantification. The uptake of L-glutamate was measured as previously described [21,22]. Briefly, cells were washed with warmed Hank's balanced salt solution (HBSS; pH 7.4) supplemented with 10 mM D-glucose.…”

“…After equilibration (15 min at 37°C in the CO 2 incubator), medium was aspirated and 500 μL of HBBS + D-Glc containing 100 μM of L-glutamate was added. After 60 minutes at 37°C, media were collected and the residual extracellular glutamate concentrations measured using the enzymatic quantification kit (Amplex ® red glutamate assay from Invitrogen) [21,22]. Glutamate secretion was measured in DMEM medium containing L-cystine (200 μM) but no phenol red or glutamate.…”

Hydrolytic Fate of 3/15-Acetyldeoxynivalenol in Humans: Specific Deacetylation by the Small Intestine and Liver Revealed Using in Vitro and ex Vivo Approaches

“…This binding causes a ribotoxic effect characterized by the activation of various protein kinases, the modulation of gene expression, leading eventually to alteration of cell functions and cell toxicity [8,9,10]. Thus, exposure to DON is associated to alterations of the intestinal, immune, and brain cell functions in animals and humans [8,10,11,12,13,14,15,16]. …”