Procyanidins B2 reverses the T-2 toxin-induced mitochondrial apoptosis in TM3 Leydig cells

Wu, Jing; Huang, Weimei; Xiao, Haisi; Yuan, Zhihang; Yi, Jine; Chen, Jingshu; Tu, Di; Yan, Tian

doi:10.1016/j.jff.2018.03.038

Cited by 14 publications

(17 citation statements)

References 38 publications

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“…In this study, T-2 toxin signi cantly decreased the expression of Nrf2 in MCF-7 cells (Fig. 2), which was consistent with the results in other cells [1,40,42]. Importantly, we found that the downregulation of Nrf2 under T-2 toxin stress is mediated by ATF3 (Fig.…”

Section: Discussionsupporting

confidence: 91%

“…Previous studies have shown that oxidative stress is a critical toxicological mechanism of T-2 toxin. In mouse Leydig cells, oxidative stress played a vital role in the T-2 toxin-induced injury, which is underpinning mechanism for T-2 toxin-induced male reproductive toxicity [41,42]. T-2 toxin treatment of N2a cells signi cantly decreased the activities of two key antioxidant enzymes SOD and CAT as well as depleting intracellular reduced GSH levels [7].…”

Section: Discussionmentioning

confidence: 99%

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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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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

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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“…The decreased antioxidant capacity causes an overproduction of reactive oxygen species (ROS), leading to damage to cellular components and heightened lipid peroxidation marked by the increases in intracellular malondialdehyde (MDA). We showed that an antioxidant in grape seed extract protects TM3 cells from the T-2 toxin-induced oxidative stresses which lead to apoptosis [22].…”

Section: Introductionmentioning

confidence: 99%

Autophagy and Apoptosis Interact to Modulate T-2 Toxin-Induced Toxicity in Liver Cells

Zhou

Yuan

et al. 2019

Toxins

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T-2 toxin is a mycotoxin generated by Fusarium species which has been shown to be highly toxic to human and animals. T-2 toxin induces apoptosis in various tissues/organs. Apoptosis and autophagy are two closely interconnected processes, which are important for maintaining physiological homeostasis as well as pathogenesis. Here, for the first time, we demonstrated that T-2 toxins induce autophagy in human liver cells (L02). We demonstrated that T-2 toxin induce acidic vesicular organelles formation, concomitant with the alterations in p62/SQSTM1 and LC3-phosphatidylethanolamine conjugate (LC3-II) and the enhancement of the autophagic flux. Using mRFP-GFP-LC3 by lentiviral transduction, we showed T-2 toxin-mediated lysosomal fusion and the formation of autophagosomes in L02 cells. The formation of autophagosomes was further confirmed by transmission electron microcopy. While T-2 toxin induced both autophagy and apoptosis, autophagy appears to be a leading event in the response to T-2 toxin treatment, reflecting its protective role in cells against cellular damage. Activating autophagy by rapamycin (RAPA) inhibited apoptosis, while suppressing autophagy by chloroquine greatly enhanced the T-2 toxin-induced apoptosis, suggesting the crosstalk between autophagy and apoptosis. Taken together, these results indicate that autophagy plays a role in protecting cells from T-2 toxin-induced apoptosis suggesting that autophagy may be manipulated for the alleviation of toxic responses induced by T-2 toxin.

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“…The oxidative stress is marked by down-regulated activity of glutathione peroxidase (GSH-Px) and catalase (CAT) with induction of the reactive oxygen species (ROS) leading to damage of cellular components as indicated by the increased in DNA damage and heightened lipid peroxidation marked by the increases in intracellular malondialdehyde (MDA). We have shown that antioxidant in grape seed extract could protect cells from T-2 toxin induced apoptosis by reducing the oxidative stresses in cells [22].…”

Section: Introductionmentioning

confidence: 96%

Crosstalk between Autophagy and Apoptosis Modulates T-2 Toxin-Induced Toxicity in Liver Cells

Wu¹,

Zhou²,

Yuan³

et al. 2018

Preprint

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T-2 toxin produced by fungi of Fusarium genus is highly toxic to human and animals and has been shown to induce apoptosis in various organs/tissues. Apoptosis and autophagy are interconnected processes and these interactions are important for cellular homeostasis as well as pathogenesis. In this study, we report for the first time that T-2 toxin induced autophagy in human liver cells (L02). We showed that T-2 toxin induced the formation of acidic vesicular organelles, concordant with the time and dose-dependent alterations in LC3-phosphatidylethanolamine conjugate (LC3-II) LC3-I/II and p62/SQSTM1 suggesting an enhanced autophagic flux. The T-2 toxin-induced formation of autophagosome and lysosomal fusion was observed by expressing mRFP-GFP-LC3 in L02 cells by lentiviral transduction, and autophagosome was observed by transmission electron microcopy. We found that while T-2 toxin activated both apoptosis and autophagy, activation of autophagy appears to be a leading event reflecting the protective mechanism of cells against the insults by T-2 toxin. Activating autophagy by rapamycin (RAPA) inhibited the apoptosis while suppressing autophagy by chloroquine greatly enhanced the T-2 toxin-induced apoptosis suggesting the crosstalk of autophagy and apoptosis. In summary, our study showed that activation of autophagy protects liver cells from T-2 toxin-induced apoptosis suggesting autophagy may be targeted for prevention of the T-2 toxin-induced toxicity in human and animals.

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Procyanidins B2 reverses the T-2 toxin-induced mitochondrial apoptosis in TM3 Leydig cells

Cited by 14 publications

References 38 publications

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

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

Autophagy and Apoptosis Interact to Modulate T-2 Toxin-Induced Toxicity in Liver Cells

Crosstalk between Autophagy and Apoptosis Modulates T-2 Toxin-Induced Toxicity in Liver Cells

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