Regulation of oxidative stress-induced cytotoxic processes of citrinin in the fission yeast Schizosaccharomyces pombe

Máté, Gábor; Gazdag, Zoltán; Mike, Nóra; Papp, Gábor; Pócsi, István; Pesti, Miklós

doi:10.1016/j.toxicon.2014.08.005

Cited by 19 publications

(19 citation statements)

References 72 publications

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“…Moreover, oxidative stress reporters are immediately upregulated upon CIT exposure and yeast mutants with a weakened antioxidant defense are hypersensitive to this mycotoxin, which altogether suggests that the induction of ROS inside cells is a primary mode of CIT action. Our result is in agreement with a previous transcriptomic assay in yeast upon prolonged CIT treatment [41] and with several studies showing CIT induced oxidative damage in diverse cellular models from yeast to humans [26,27,28,30]. As a consequence, external addition of antioxidants usually alleviates CIT toxicity [25,48,49].…”

Section: Discussionsupporting

confidence: 92%

“…Much less is known about the toxicity mechanisms of CIT, however, it has been shown to be an efficient nephrotoxin as well [22]. Several groups have contributed to the identification of possible molecular mechanisms of CIT toxicity, finding, among other consequences, the increase of oxidative stress in connection with alterations of mitochondrial function, and induction of apoptosis [23,24,25,26,27,28,29,30,31]. It has been proposed that the co-occurrence of both toxins results in synergetic effects, however no clear conclusions have been reached [32,33].…”

Section: Introductionmentioning

confidence: 99%

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Different Toxicity Mechanisms for Citrinin and Ochratoxin A Revealed by Transcriptomic Analysis in Yeast

Vanacloig-Pedros

Proft

Pascual-Ahuir

2016

Toxins

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Citrinin (CIT) and ochratoxin A (OTA) are important mycotoxins, which frequently co-contaminate foodstuff. In order to assess the toxicologic threat posed by the two mycotoxins separately or in combination, their biological effects were studied here using genomic transcription profiling and specific live cell gene expression reporters in yeast cells. Both CIT and OTA cause highly transient transcriptional activation of different stress genes, which is greatly enhanced by the disruption of the multidrug exporter Pdr5. Therefore, we performed genome-wide transcription profiling experiments with the pdr5 mutant in response to acute CIT, OTA, or combined CIT/OTA exposure. We found that CIT and OTA activate divergent and largely nonoverlapping gene sets in yeast. CIT mainly caused the rapid induction of antioxidant and drug extrusion-related gene functions, while OTA mainly deregulated developmental genes related with yeast sporulation and sexual reproduction, having only a minor effect on the antioxidant response. The simultaneous exposure to CIT and OTA gave rise to a genomic response, which combined the specific features of the separated mycotoxin treatments. The application of stress-specific mutants and reporter gene fusions further confirmed that both mycotoxins have divergent biological effects in cells. Our results indicate that CIT exposure causes a strong oxidative stress, which triggers a massive transcriptional antioxidant and drug extrusion response, while OTA mainly deregulates developmental genes and only marginally induces the antioxidant defense.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Different Toxicity Mechanisms for Citrinin and Ochratoxin A Revealed by Transcriptomic Analysis in Yeast

Vanacloig-Pedros

Proft

Pascual-Ahuir

2016

Toxins

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“…Therefore, the neuroprotective effect of citrinin against glutamate induced excitotoxicity can not be explained by the prevention of calcium overload. There have been repeated reports that high-dose citrinin application induces the production of ROS and subsequent cell death (Chen and Chan, 2009;Kumar et al, 2011;Máté et al, 2014). Conversely, citrinin and its predicted precursor and metabolites have been reported as antioxidants (Li et al, 2006;Zhang et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Low doses of the mycotoxin citrinin protect cortical neurons against glutamate-induced excitotoxicity

et al. 2016

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-Citrinin, a natural mycotoxin that is found in fermented foods, is known as a cytotoxin and nephrotoxin. Exposure to high doses of citrinin result in apoptosis; however, the effects of low doses are not fully understood. Glutamate excitotoxicity is responsible for neuronal death in acute neurological disorders including stroke, trauma and other neurodegenerative diseases. Here, we show the neuroprotective effect of low doses of citrinin against glutamate-induced excitotoxicity. We examined the effect of citrinin exposure on glutamate-induced cell death in cultured rat cortical neurons under two conditions: simultaneous treatment with citrinin 0.1 to 1,000 nM and glutamate (30 μM) for 1, 3 hr; the same simultaneous treatment for 3 hr after pretreatment with citrinin for 21 hr. Both the MTT and immunocytochemical assay showed significant neuroprotective effects at several doses and exposure times tested. All concentrations of citrinin tested showed no remarkable cell death following 14-day exposure, and no marked alterations to synapses. These data suggest that low doses of citrinin can be used as a neuroprotective agent against glutamate-induced excitotoxicity without additional harmful cellular alterations.

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“…And the results showed that the oocytes exposure to citrinin toxin suffered the early apoptosis. Citrinin was shown to affect ROS level in different models, such as fission yeast [23], HepG2 cell [24] and mouse skin [25]. While besides citrinin, the other mycotoxins, like ZEN, HT-2 toxin were all reported to cause the oxidative stress, which was indicated as ROS level [4, 11].…”

Section: Discussionmentioning

confidence: 99%

Citrinin exposure affects oocyte maturation and embryo development by inducing oxidative stress-mediated apoptosis

Zhang

et al. 2017

Oncotarget

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Citrinin is one of the mycotoxins and has been shown to have various toxic effects in animals and humans. Although previous study showed the toxic effects of citrinin on the female reproductive system, especially on oocyte maturation, however, the causes or mechanism of citrinin on oocyte quality is unclear. In present study we deeply investigated this topic. We found thatcitrinin toxin exposure inhibited mouse oocyte maturation and early embryo development. Further investigation showed that the actin distribution in oocytes and embryos was disrupted, and the reduced expression of actin nucleator ARP2 expression in the oocyte cortex further confirmed this. We also found that meiotic spindle morphology was abnormal after citrinin treatment. These results indicated that citrinin toxin exposure could disrupt cytoskeleton dynamics to affect oocyte maturation and early embryo development. We also examined the ROS level and early apoptosis marker Annexin signals, and the results showed that both levels increased, indicating that citrinin induced oxidative stress and further resulted in oocyte early apoptosis. Taken together, our results indicated that citrinin toxin exposure could reduce mouse oocyte maturation and early embryo development capability by affecting cytoskeletal dynamics, which may be due to the oxidative stress induced early apoptosis.

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Regulation of oxidative stress-induced cytotoxic processes of citrinin in the fission yeast Schizosaccharomyces pombe

Cited by 19 publications

References 72 publications

Different Toxicity Mechanisms for Citrinin and Ochratoxin A Revealed by Transcriptomic Analysis in Yeast

Different Toxicity Mechanisms for Citrinin and Ochratoxin A Revealed by Transcriptomic Analysis in Yeast

Low doses of the mycotoxin citrinin protect cortical neurons against glutamate-induced excitotoxicity

Citrinin exposure affects oocyte maturation and embryo development by inducing oxidative stress-mediated apoptosis

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