EGR1 is essential for deoxynivalenol-induced G2/M cell cycle arrest in HepG2 cells via the ATF3ΔZip2a/2b-EGR1-p21 pathway

Yuan, Liping; Mu, Peiqiang; Huang, Boyen; Li, Hui; Mu, Haibin; Deng, Yiqun

doi:10.1016/j.toxlet.2018.09.012

Cited by 29 publications

(20 citation statements)

References 36 publications

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“…For all cell lines, we observed a decrease in the number of cells in the G0/G1 cell cycle phase with a simultaneous increase in the number of cells in the S and G2/M cell cycle phase. A similar increase in the number of cells in G2/M cell cycle phase was observed by Yuan et al in HepG2 cells treated with DON at doses of 2 and 4 µg/mL [26]. The changes in the cell cycle caused by DON were also observed by Lei at al., though they observed the cell cycle arrest in the G0/G1 cell cycle phase in human chondrocyte, hepatic epithelial and tubular epithelial cells [41].…”

Section: Discussionsupporting

confidence: 80%

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Deoxynivalenol Modulates the Viability, ROS Production and Apoptosis in Prostate Cancer Cells

Habrowska-Górczyńska

Kowalska

Urbanek

et al. 2019

Toxins

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Deoxynivalenol (DON), known as vomitoxin, a type B trichothecene, is produced by Fusarium. DON frequently contaminates cereal grains such as wheat, maize, oats, barley, rye, and rice. At the molecular level, it induces ribosomal stress, inflammation and apoptosis in eukaryotic cells. Our findings indicate that DON modulates the viability of prostate cancer (PCa) cells and that the response to a single high dose of DON is dependent on the androgen-sensitivity of cells. DON appears to increase reactive oxygen species (ROS) production in cells, induces DNA damage, and triggers apoptosis. The effects of DON application in PCa cells are influenced by the mitogen-activated protein kinase (MAPK) and NFΚB- HIF-1α signaling pathways. Our results indicate that p53 is a crucial factor in DON-associated apoptosis in PCa cells. Taken together, our findings show that a single exposure to high concentrations of DON (2–5 µM) modulates the progression of PCa.

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Section: Discussionsupporting

confidence: 80%

“…22Rv1 cells were isolated from a xenograft and are positive for AR and PSA only at the mRNA level. The tested doses of DON (0.0001–40 µM) were based on previous studies conducted on cancer cells [25,26].…”

Section: Resultsmentioning

confidence: 99%

Deoxynivalenol Modulates the Viability, ROS Production and Apoptosis in Prostate Cancer Cells

Habrowska-Górczyńska

Kowalska

Urbanek

et al. 2019

Toxins

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“…Those resulting in transcriptional activation or repression are observed near the Pparγ2 promoter in adipocytes [ 24 ]. It has been reported that the enrichment of H3K9ac and H3K27ac in promoter regions is affected by DON administration [ 57 ]. Interestingly, we found that the inhibitory effect of DON on the expression of PPARγ2 was mediated by inhibiting H3K4me2 and H3K4me3 enrichment instead of that of H3K9ac and H3K27ac at the promoter of Pparγ2 in 3T3-L1 cells.…”

Section: Discussionmentioning

confidence: 99%

Deoxynivalenol Exposure Suppresses Adipogenesis by Inhibiting the Expression of Peroxisome Proliferator-Activated Receptor Gamma 2 (PPARγ2) in 3T3-L1 Cells

Zhao

Tang

Lin

et al. 2020

IJMS

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Deoxynivalenol (DON)—a type B trichothecene mycotoxin, mainly produced by the secondary metabolism of Fusarium—has toxic effects on animals and humans. Although DON’s toxicity in many organs including the adrenal glands, thymus, stomach, spleen, and colon has been addressed, its effects on adipocytes have not been investigated. In this study, 3T3-L1 cells were chosen as the cell model and treated with less toxic doses of DON (100 ng/mL) for 7 days. An inhibition of adipogenesis and decrease in triglycerides (TGs) were observed. DON exposure significantly downregulated the expression of PPARγ2 and C/EBPα, along with that of other adipogenic marker genes in 3T3-L1 cells and BALB/c mice. The anti-adipogenesis effect of DON and the downregulation of the expression of adipogenic marker genes were effectively reversed by PPARγ2 overexpression. The repression of PPARγ2′s expression is the pivotal event during DON exposure regarding adipogenesis. DON exposure specifically decreased the di-/trimethylation levels of Histone 3 at lysine 4 in 3T3-L1 cells, therefore weakening the enrichment of H3K4me2 and H3K4me3 at the Pparγ2 promoter and suppressing its expression. Conclusively, DON exposure inhibited PPARγ2 expression via decreasing H3K4 methylation, downregulated the expression of PPARγ2-regulated adipogenic marker genes, and consequently suppressed the intermediate and late stages of adipogenesis. Our results broaden the current understanding of DON’s toxic effects and provide a reference for addressing the toxicological mechanism of DON’s interference with lipid homeostasis.

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“…ATF3 is an important oxidative stress induced transcriptional factor that has been shown to activate or repress various oxidative stress responsive genes [36]. Our previous study showed that a structural similar mycotoxin, deoxynivalenol, signi cantly induced the expression of one variant of ATF3, ATF3ΔZip2a/2b [37]. Interestingly, the expression of ATF3∆Zip2a/2b was also signi cantly upregulated by T-2 toxin in MCF-7 cells (Fig.…”

Section: Atf3∆zip2a/2b Was Involved In the T-2 Toxin-induced Ros Accumulationmentioning

confidence: 92%

T-2 Toxin Induces Oxidative Stress at Low Doses Via ATF3∆Zip2a/2b-Mediated Ubiquitination and Degradation of Nrf2

Chen

Zhu

et al. 2021

Preprint

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Background: T-2 toxin is mainly produced by Fusarium species, which is an extremely toxic mycotoxin to humans and animals. It is well known that T-2 toxin induces oxidative stress, but the molecular mechanism is still unknown. Results: In this study, we found that T-2 toxin significantly promoted ROS accumulation in MCF-7 cells at low doses which maintains cell viability at least 80%. Further analysis showed that T-2 toxin downregulated the expression of the master regulator of antioxidant defense gene, Nrf2, and its targeted antioxidant genes. Overexpression of Nrf2 or its target gene HO1 significantly blocked the ROS accumulation in MCF-7 cells under T-2 toxin treatment. Moreover, we found that T-2 toxin downregulated the antioxidant genes via inducing the expression of ATF3∆Zip2a/2b. Importantly, overexpression of ATF3∆Zip2a/2b promoted the ubiquitination and degradation of Nrf2. Conclusions: This work demonstrated that T-2 toxin induced ROS accumulation via ATF3∆Zip2a/2b mediated ubiquitination and degradation of Nrf2, which provided a new insight into the mechanism of T-2 toxin-induced oxidative stress.

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EGR1 is essential for deoxynivalenol-induced G2/M cell cycle arrest in HepG2 cells via the ATF3ΔZip2a/2b-EGR1-p21 pathway

Cited by 29 publications

References 36 publications

Deoxynivalenol Modulates the Viability, ROS Production and Apoptosis in Prostate Cancer Cells

Deoxynivalenol Modulates the Viability, ROS Production and Apoptosis in Prostate Cancer Cells

Deoxynivalenol Exposure Suppresses Adipogenesis by Inhibiting the Expression of Peroxisome Proliferator-Activated Receptor Gamma 2 (PPARγ2) in 3T3-L1 Cells

T-2 Toxin Induces Oxidative Stress at Low Doses Via ATF3∆Zip2a/2b-Mediated Ubiquitination and Degradation of Nrf2

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