Mitochondrial proteomic analysis reveals the molecular mechanisms underlying reproductive toxicity of zearalenone in MLTC-1 cells

Li, Yuzhe; Zhang, Boyang; Huang, Kunlun; He, Xiaoyun; Luo, Yunbo; Liang, Rui; Luo, Hanpeng; Shen, Xiao Li; Xu, Wentao

doi:10.1016/j.tox.2014.07.007

Cited by 38 publications

(27 citation statements)

References 80 publications

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“…We investigated the expression of peroxisome proliferator activated receptors (PPARs), since ZEN exposure can increase energy production through an increase in the uptake and β-oxidation of fatty acids, in a processes that has been suggested to be mediated by activation of PPARs in Leydig cells [40]. However, we observed no changes in PPARα or in PPARγ gene expression at any timepoint.…”

Section: Effect Of Zearalenone On Cytokine Inflammatory Markers Andmentioning

confidence: 84%

“…We investigated the expression of PPARα, PPARγ as well as that of other genes linked with adipokines, a family of metabolic sensing proteins, of which some members have been found to be regulated by ZEN in the intestine [30,40]. No differences in the expression of PPARα, PPARγ, serum amyloid A, lipocalin 2 or adiponectin were found, whereas the mRNA levels of the adipokines receptors for adiponectin (AdipoR2), resistin (CAP1) and chemerin (CMKLR1) were significantly up-regulated.…”

Section: Discussionmentioning

confidence: 99%

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Acute Exposure to Zearalenone Disturbs Intestinal Homeostasis by Modulating the Wnt/β-Catenin Signaling Pathway

Lahjouji

Bertaccini

Neves

et al. 2020

Toxins

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The mycotoxin zearalenone (ZEN), which frequently contaminates cereal-based human food and animal feed, is known to have an estrogenic effect. The biological response associated with exposure to ZEN has rarely been reported in organs other than the reproductive system. In the intestine, several studies suggested that ZEN might stimulate molecular changes related to the activation of early carcinogenesis, but the molecular mechanisms behind these events are not yet known. In this study, we investigated gene expression and changes in protein abundance induced by acute exposure to ZEN in the jejunum of castrated male pigs using an explant model. Our results indicate that ZEN induces the accumulation of ERα but not ERβ, modulates Wnt/β-catenin and TGF-β signaling pathways, and induces molecular changes linked with energy sensing and the antimicrobial activity without inducing inflammation. Our results confirm that the intestine is a target for ZEN, inducing changes that promote cellular proliferation and could contribute to the onset of intestinal pathologies. Key Contribution:The consequences of the estrogen-disrupting activity of ZEN in the small intestine were investigated. Our results indicate that acute exposure to ZEN promotes changes in signaling pathways that are important for the intestinal physiology such as estrogen, Wnt/β-catenin and TGF-β as well as changes in the expression of metabolic sensing molecules and antimicrobial proteins.ZEN is more dependent on the activation of the estrogen receptor (ER) signaling pathway, which has an anti-inflammatory [8,11,12], anti-apoptotic and proliferating effect [3,13,14]. ER is a ligand-activated transcriptional factor, and signaling is mainly activated directly upon DNA binding in the estrogen response elements located in target genes, but also indirectly (not involving DNA binding) through interaction with other signaling pathways [15][16][17]. There are two types of ERs, ERα and ERβ, whose roles differ. ERα is the main regulator of estrogen-dependent genes and its activation has proliferative effects. ERβ, when co-expressed with ERα, tends to restrain ERα activity and its activation inhibits cell proliferation [18]. ZEN can activate both ERs but is a partial agonist of ERβ and a full agonist of ERα [19]. Consequently, the biological response to exposure to ZEN varies depending on the tissue-specific ratio of the ER α vs. β, as well as on the density of these receptors [20]. In the intestine, the presence of each ER is distributed differently along the crypt-villus axis, ERα being more abundant in the crypt (where cell proliferation occurs) while ERβ is more abundant in the villi (composed of differentiated enterocytes) [21,22]. Estrogen signaling interacts with other pathways that are important for intestinal homeostasis and its disruption seems to relate to the development of chronic intestinal diseases and cancer [23][24][25]. As the intestine is an estrogen-responding organ, it is important to understand the molecular effect of natural endocrine disruptors suc...

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Section: Effect Of Zearalenone On Cytokine Inflammatory Markers Andmentioning

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Acute Exposure to Zearalenone Disturbs Intestinal Homeostasis by Modulating the Wnt/β-Catenin Signaling Pathway

Lahjouji

Bertaccini

Neves

et al. 2020

Toxins

View full text Add to dashboard Cite

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“…Cells were then transferred to a 96-well microplate and analyzed. DCFH-DA fluorescent probe converted to DCF [ 32 ] reveals reactive oxygen species levels by green fluorescence at an emission wavelength of 535 nm and excitation wavelength of 485 nm using the fluorostar Optima (BMG, Ortenberg, Germany) fluorescence reader. Results (percent, %) were shown as negative control standardization.…”

Section: Methodsmentioning

confidence: 99%

Xylazine as a Drug of Abuse and Its Effects on the Generation of Reactive Species and DNA Damage on Human Umbilical Vein Endothelial Cells

Silva-Torres

Vélez

Álvarez

et al. 2014

Journal of Toxicology

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Human xylazine (XYL) abuse among addicts has received great interest due to its potential toxic effects upon addicts and the need to understand the mechanism of action associated with the potential health effects. XYL is an alpha-2 agonist restricted to veterinarian applications, without human medical applications. Our previous work demonstrated that XYL and its combination with cocaine (COC) and/or 6-monoacetylmorphine (6-MAM) induce cell death through an apoptotic mechanism. The aim of this study was to determine the effect of xylazine on the generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) as well as DNA damage on endothelial cell. Human umbilical vein endothelial cells (HUVEC) were treated with XYL (60 μM), COC (160 μM), 6-MAM (160 μM), camptothecin (positive control, 50 μM), XYL/COC (50 μM), XYL/6-MAM (50 μM), and XYL/COC/6-MAM (40 μM) for a period of 24 hours. Generation of intracellular ROS, RNS, and DNA fragmentation were analyzed using a fluorometric assay. Results reveal that XYL and 6-MAM increase levels of ROS; no induction of RNS production was observed. The combination of these drugs shows significant increase in DNA fragmentation in G2/M phase, while XYL, COC, and 6-MAM, without combination, present higher DNA fragmentation in G0/G1 phase. These findings support that these drugs and their combination alter important biochemical events aligned with an apoptotic mechanism of action in HUVEC.

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“…In the last 10 years proteomics has been used either to build a knowledgebase [81] or investigate how different environmental or artificial conditions during fungal growth can modulate fungi stress response [82][83][84] or proteome changes during mycotoxin producing conditions [85][86][87][88]. Recently, several proteomic-based studies have been made to investigate how mycotoxins can modulate immunity in vitro [89,90], mitochondrial dynamics [91], or induce selective toxicity [92][93][94][95].…”

Section: Fungimentioning

confidence: 99%

Proteomics in food: Quality, safety, microbes, and allergens

et al. 2016

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Food safety and quality and their associated risks pose a major concern worldwide regarding not only the relative economical losses but also the potential danger to consumer's health. Customer's confidence in the integrity of the food supply could be hampered by inappropriate food safety measures. A lack of measures and reliable assays to evaluate and maintain a good control of food characteristics may affect the food industry economy and shatter consumer confidence. It is imperative to create and to establish fast and reliable analytical methods that allow a good and rapid analysis of food products during the whole food chain. Proteomics can represent a powerful tool to address this issue, due to its proven excellent quantitative and qualitative drawbacks in protein analysis. This review illustrates the applications of proteomics in the past few years in food science focusing on food of animal origin with some brief hints on other types. Aim of this review is to highlight the importance of this science as a valuable tool to assess food quality and safety. Emphasis is also posed in food processing, allergies, and possible contaminants like bacteria, fungi, and other pathogens.

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Mitochondrial proteomic analysis reveals the molecular mechanisms underlying reproductive toxicity of zearalenone in MLTC-1 cells

Cited by 38 publications

References 80 publications

Acute Exposure to Zearalenone Disturbs Intestinal Homeostasis by Modulating the Wnt/β-Catenin Signaling Pathway

Acute Exposure to Zearalenone Disturbs Intestinal Homeostasis by Modulating the Wnt/β-Catenin Signaling Pathway

Xylazine as a Drug of Abuse and Its Effects on the Generation of Reactive Species and DNA Damage on Human Umbilical Vein Endothelial Cells

Proteomics in food: Quality, safety, microbes, and allergens

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