Inhibitors of apoptosis proteins (IAPs) are associated with T-2 toxin-induced decreased collagen II in mouse chondrocytes in vitro

Ji, Yi; Yang, Wenjing; Zhang, Chengzhi; Angwa, Linet Musungu; Jin, Baiming; Liu, Juan; Lv, Man; Ma, Wenjing; Yang, Jie; Wang, Kewei

doi:10.1016/j.toxicon.2020.01.002

Cited by 12 publications

(4 citation statements)

References 28 publications

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“…As one of the most acutely toxic trichothecene species, T-2 toxin damages the digestive, nervous, and reproductive systems of both animals and humans . T-2 toxin is thought to increase the production of oxygen radicals, overwhelming the scavenging system and resulting in cell injury, autophagy, and immunosuppression. , T-2 toxin induces oxidative stress by activating multiple signaling pathways, including the mitogen-activated protein kinase (MAPK) pathway, ribose toxic stress response pathway, mitochondrial-mediated oxidative stress pathway, , and the Janus tyrosine kinase–signal transducer and activator of transcription pathway. , In addition, oxidative damage triggers apoptosis by altering the expression of the Bcl-2 family, caspase family, and p53 proteins …”

Section: Introductionmentioning

confidence: 99%

T-2 Toxin Induces Ferroptosis by Increasing Lipid Reactive Oxygen Species (ROS) and Downregulating Solute Carrier Family 7 Member 11 (SLC7A11)

Wang

Qin

Zheng

et al. 2021

J. Agric. Food Chem.

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T-2 toxin is a trichothecene mycotoxin commonly found in animal feed and agricultural products. Evidence indicates that T-2 toxin induces apoptosis and autophagy. This study investigated the role of ferroptosis in T-2 toxin cytotoxicity. RASselective lethal compound 3 (RSL3) and Erastin were applied to initiate ferroptosis. RSL3-and Erastin-initiated cell death were enhanced by T-2 toxin. Treatment with the ferroptosis inhibitor ferrostatin-1 markedly restored the sensitizing effect of T-2 toxin to RSL3-or Erastin-initiated apoptosis, suggesting that ferroptosis plays a vital role in T-2 toxin-induced cytotoxicity. Mechanistically, T-2 toxin promoted ferroptosis by inducing lipid reactive oxygen species (ROS), as N-acetyl-L-cysteine significantly blocked T-2 toxin-induced ferroptosis. Moreover, T-2 toxin decreased the expression of solute carrier family 7 member 11 (SLC7A11) and failed to further enhance ferroptosis in SLC7A11-deficient cells. SLC7A11 overexpression significantly rescued the enhanced ferroptosis caused by T-2 toxin. T-2 toxin induces ferroptosis by downregulating SLC7A11 expression. Ferroptosis mediates T-2 toxin-induced cytotoxicity by increasing ROS and downregulating SLC7A11 expression.

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Section: Introductionmentioning

confidence: 99%

T-2 Toxin Induces Ferroptosis by Increasing Lipid Reactive Oxygen Species (ROS) and Downregulating Solute Carrier Family 7 Member 11 (SLC7A11)

Wang

Qin

Zheng

et al. 2021

J. Agric. Food Chem.

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“…Apoptosis can be initiated by the mitochondrial apoptosis pathway (caspase-3). It has been confirmed that inhibitors of apoptosis proteins (IAPs) are involved in the T-2-induced decrease in collagen II (Wang et al 2020b). These results suggest that T-2 induces apoptosis through a mitochondria-mediated pathway.…”

Section: Autophagy and Apoptosismentioning

confidence: 79%

An update on T-2 toxin and its modified forms: metabolism, immunotoxicity mechanism, and human exposure assessment

Qin

Kuča

et al. 2020

Arch Toxicol

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T-2 toxin is the most toxic trichothecene mycotoxin, and it exerts potent toxic effects, including immunotoxicity, neurotoxicity, and reproductive toxicity. Recently, several novel metabolites, including 3′,4′-dihydroxy-T-2 toxin and 4′,4′-dihydroxy-T-2 toxin, have been uncovered. The enzymes CYP3A4 and carboxylesterase contribute to T-2 toxin metabolism, with 3′-hydroxy-T-2 toxin and HT-2 toxin as the corresponding primary products. Modified forms of T-2 toxin, including T-2-3-glucoside, exert their immunotoxic effects by signaling through JAK/STAT but not MAPK. T-2-3-glucoside results from hydrolyzation of the corresponding parent mycotoxin and other metabolites by the intestinal microbiota, which leads to enhanced toxicity. Increasing evidence has shown that autophagy, hypoxia-inducible factors, and exosomes are involved in T-2 toxin-induced immunotoxicity. Autophagy promotes the immunosuppression induced by T-2 toxin, and a complex crosstalk between apoptosis and autophagy exists. Very recently, "immune evasion" activity was reported to be associated with this toxin; this activity is initiated inside cells and allows pathogens to escape the host immune response. Moreover, T-2 toxin has the potential to trigger hypoxia in cells, which is related to activation of hypoxia-inducible factor and the release of exosomes, leading to immunotoxicity. Based on the data from a series of human exposure studies, free T-2 toxin, HT-2 toxin, and HT-2-4-glucuronide should be considered human T-2 toxin biomarkers in the urine. The present review focuses on novel findings related to the metabolism, immunotoxicity, and human exposure assessment of T-2 toxin and its modified forms. In particular, the immunotoxicity mechanisms of T-2 toxin and the toxicity mechanism of its modified form, as well as human T-2 toxin biomarkers, are discussed. This work will contribute to an improved understanding of the immunotoxicity mechanism of T-2 toxin and its modified forms. Keywords T-2 toxin • Modified T-2 toxin • Metabolism • Immunotoxicity • Human exposure assessments • Biomarkers Abbreviations AhR Aryl hydrocarbon receptor AKNA AT-hook transcriptionfactor Akt Serine/threonine protein kinase ARE Antioxidant response element CREB CAMP-response clement-binding protein CYP450 Cytochrome P450 DAS Diacetoxyscirpenol DRP-1 Dynamin-related protein 1 DON Deoxynivalenol D3G Deoxynivalenol-3-glucoside ECM Extracellular matrix EIF2AK2 Double-stranded RNA-activated protein kinase ERK Etracellular signaling kinase FXR Farnesoid X receptor GH Growth hormone Qinghua Wu and Zihui Qin contributed equally to this work.

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“…T-2 toxin was detected from the food flour of patient households in KBD area and the content of T-2 toxin was higher than that of commercial market flour in the non-sick areas. Accordingly, the T-2 toxin of grains in the disease area below 100 μg/kg or at least below 300 μg/kg is a measure to block the occurrence of KBD; (2) Feeding chicks with 100 ng/ kg•day of pure T-2 toxin in the feed for 3-5 weeks could cause pathological changes analogous to human KBD, resembling the result of using Fusarium bacteria mixed with chicken feed at a ratio of 1/10; (3) T-2 toxin could apparently inhibit the proliferation of chondrocytes in a dose-dependent manner [18] ;…”

Section: T-2 Toxinmentioning

confidence: 99%

Cold weather and Kashin-Beck disease

Wang

Sun

2023

Frigid Zone Medicine

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Kashin-Beck disease (KBD) is an endemic osteoarthropathy. Its distribution region covers a long and narrow belt on the Pacific side and belongs to continental climate with short summer, long frost period, and large temperature differences between day and night. In particular, KBD patients are typically scattered in the rural areas with seasonal features such as cold winters and rainy autumns. Etiological studies have demonstrated that the carrier of pathogenic factors is the grains produced in endemic areas. Risk factors for KBD include fungal contamination of grains due to poor storage conditions associated with cold weather. The epidemiological characteristics of KBD include agricultural area, early age of onset, gender equality, family aggregation, regional differences, and annual fluctuations. A series of preventive measures have been successfully taken in the past decades. National surveillance data indicate that the annual incidence of KBD is gradually declining.

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Inhibitors of apoptosis proteins (IAPs) are associated with T-2 toxin-induced decreased collagen II in mouse chondrocytes in vitro

Cited by 12 publications

References 28 publications

T-2 Toxin Induces Ferroptosis by Increasing Lipid Reactive Oxygen Species (ROS) and Downregulating Solute Carrier Family 7 Member 11 (SLC7A11)

T-2 Toxin Induces Ferroptosis by Increasing Lipid Reactive Oxygen Species (ROS) and Downregulating Solute Carrier Family 7 Member 11 (SLC7A11)

An update on T-2 toxin and its modified forms: metabolism, immunotoxicity mechanism, and human exposure assessment

Cold weather and Kashin-Beck disease

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