The food-associated fungal neurotoxin ochratoxin A inhibits the absorption of glutamate by astrocytes through a decrease in cell surface expression of the excitatory amino-acid transporters GLAST and GLT-1

Razafimanjato, Helisoa; Garmy, Nicolas; Guo, Xiaojun; Varini, Karine; Scala, Coralie Di; Pasquale, Eric Di; Taïeb, Nadira; Maresca, Marc

doi:10.1016/j.neuro.2010.06.003

Cited by 44 publications

(35 citation statements)

References 59 publications

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“…Primary cortical glial cell cultures were prepared from cerebral cortices of 0-to 4-day-old Wistar rats using standard protocol (H€ oltje et al, 2008;Razafimanjato et al, 2010;Solà et al, 2002). After removal of meninges, cortices were washed with phosphate buffer saline (PBS) supplemented with 1% antibiotics.…”

Section: Materials and Methods Cell Cultures And Treatmentmentioning

confidence: 99%

“…Glutamate uptake by enriched cortical astrocytes seeded onto 12-well plates was measured as previously described (Razafimanjato et al, 2010). After DON treatment, cells were washed with Hank's balanced salt solution (HBSS; pH 7.4) supplemented with 10 mM D-glucose.…”

Section: Uptake Of L-glutamate By Astrocytesmentioning

confidence: 99%

“…Activity of GS was measured as previously explained (Razafimanjato et al, 2010). Briefly, primary astrocytes seeded onto 12-well plates were lysed in PBS containing 1% Triton X100 and protease inhibitor cocktail at 4°C.…”

Section: Glutamine Synthetase Assaymentioning

confidence: 99%

“…Surface expression of EAAT by primary astrocytes was evaluated as previously described (Razafimanjato et al, 2010). Astrocytes seeded onto 6-well plates were either left untreated or treated with DON before surface biotinylation.…”

Section: Cell Surface Expression Of Eaatmentioning

confidence: 99%

“…Previous studies have already shown that various fungal toxins or mycotoxins (mainly fumonisins, ochratoxins, and trichothecenes) are able to directly cause brain cell death (Belmadani et al, 1999;Bruinink et al, 1998;Corps et al, 2010;Islam et al, 2009;Kwon et al, 2000;Merrill et al, 1996;Osuchowski and Sharma, 2005;Pestka et al, 2008a;Purzycki and Shain, 2010;Sava et al, 2006;Zhang et al, 2009). However, only few evaluations have been conducted on the potential effect of mycotoxins on the functions of glial cells (Monnet-Tschudi et al, 1997;Razafimanjato et al, 2010;Zurich et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

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The ribotoxin deoxynivalenol affects the viability and functions of glial cells

Razafimanjato

Benzaria

Taïeb

et al. 2011

Glia

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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.

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Section: Materials and Methods Cell Cultures And Treatmentmentioning

confidence: 99%

Section: Uptake Of L-glutamate By Astrocytesmentioning

confidence: 99%

Section: Glutamine Synthetase Assaymentioning

confidence: 99%

Section: Cell Surface Expression Of Eaatmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

The ribotoxin deoxynivalenol affects the viability and functions of glial cells

Razafimanjato

Benzaria

Taïeb

et al. 2011

Glia

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Investigation of the mechanisms behind ochratoxin A‐induced cytotoxicity in human astrocytes and the protective effects of N‐acetylcysteine

Chu,

Chen,

Liang

2024

J of Applied Toxicology

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Ochratoxin A (OTA) is a type of mycotoxin commonly found in raw and processed foods. It is essential to be aware of this toxin, as it can harm your health if consumed in high quantities. OTA can induce toxic effects in various cell models. However, a more comprehensive understanding of the harmful effects of OTA on human astrocytes is required. This study evaluated OTA's neurotoxic effects on the Gibco® Human Astrocyte (GHA) cell line, its underlying mechanisms, and the antioxidant N‐acetylcysteine (NAC) ability to prevent them. OTA exposure within 5–30 μM has induced concentration‐dependent cytotoxicity. In the OTA‐treated cells, the levels of reactive oxygen species (ROS) were found to be significantly increased, while the glutathione (GSH) contents were found to decrease considerably. The western blotting of OTA‐treated cells has revealed increased Bax, cleaved caspase‐9/caspase‐3 protein levels, and increased Bax/Bcl‐2 ratio. In addition, exposure to OTA has resulted in the induction of antioxidant responses associated with the protein expressions of Nrf2, HO‐1, and NQO1. On the other hand, the pretreatment with NAC has partially alleviated the significant toxic effects of OTA. In conclusion, our findings suggest that oxidative stress and apoptosis are involved in the OTA‐induced cytotoxicity in GHA cells. NAC could act as a protective agent against OTA‐induced oxidative damage.

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Deoxynivalenol inhibits the expression by goblet cells of intestinal mucins through a PKR and MAP kinase dependent repression of the resistin‐like molecule β

Pinton

Graziani

Pujol

et al. 2015

Molecular Nutrition Food Res

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Taken together, our results show that at low doses found in food and feed, DON is able to affect the expression and production of MUCs by human and animal goblet cells. Due to the important role of MUCs in the barrier function and in the interaction of commensal bacteria with the host, such effect could explain the observed modifications in the microbial diversity and the increased susceptibility to enteric infection following exposure to DON.

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The food-associated fungal neurotoxin ochratoxin A inhibits the absorption of glutamate by astrocytes through a decrease in cell surface expression of the excitatory amino-acid transporters GLAST and GLT-1

Cited by 44 publications

References 59 publications

The ribotoxin deoxynivalenol affects the viability and functions of glial cells

The ribotoxin deoxynivalenol affects the viability and functions of glial cells

Investigation of the mechanisms behind ochratoxin A‐induced cytotoxicity in human astrocytes and the protective effects of N‐acetylcysteine

Deoxynivalenol inhibits the expression by goblet cells of intestinal mucins through a PKR and MAP kinase dependent repression of the resistin‐like molecule β

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