Study on the Apoptosis Mechanism Induced by T-2 Toxin

Abstract

T-2 toxin is known to induce apoptosis in mammalian cells. The mechanism of apoptosis induced by T-2 toxin has been proposed to be linked with oxidative stress and mitochondrial pathway. In the current study, the toxic effect of T-2 on Hela, Bel-7402, and Chang liver cells was examined in dose-dependent and time-dependent manner by MTT assay. Caspase-3 was found to be up-regulated under T-2 toxin stress, which suggested that T-2 toxin induced cell apoptosis. Endogenous GSH and MDA levels in all three cell lines were found down- and up-regulated respectively, which indicated the link between toxic effect of T-2 toxin and intracellular oxidative stress. It was also found by MTT assay that NAC, which maintained the level of GSH in cells, could protect cells from death. Western-blot result showed that the level of both activated Caspase-8 and Caspase-9 increased when cells were treated by T-2 toxin. Caspase-9 was found to be activated earlier than Caspase-8. It was also found that p53 was up-regulated under T-2 toxin stress in the study. These results implied that the effect of T-2 toxin on cells was apoptosis rather than necrosis, and it was probably induced through mitochondrial pathway. To the best of our knowledge, the present study is the first to show that JunD is down-regulated in T-2 toxin induced apoptosis. By construction of an over-expression vector for the JunD gene, we observed that the survival ratio of JunD over-expressed cells obviously increased under T-2 toxin stress. These results suggested that the mechanism of T-2 induced cell death was closely connected with oxidative stress, and that JunD plays an important role in the defensive process against T-2 toxin stress.

Endoplasmic reticulum stress is involved in the T‐2 toxin‐induced apoptosis in goat endometrium epithelial cells

“…The mitochondria, death receptor and ER‐mediated apoptotic pathways are the three key pathways involved in apoptosis in mammalian cells (Wang et al, ). Zhuang, Yang, Huang, and Wang () reported that the mechanism of apoptosis induced by the T‐2 toxin was linked with oxidative stress and the mitochondrial pathway in Hela, Bel‐7402 and Chang liver cells. In this study, an increased cleaved‐caspase‐3 protein expression was observed upon T‐2 toxin exposure (Figure C).…”

T‐2 toxin downregulates LHCGR expression, steroidogenesis, and cAMP level in human cumulus granulosa cells

“…5 T-2 toxin exposure induces lesions in hematopoietic, lymphoid, gastrointestinal, and brain tissue. [6][7][8] Also, T-2 toxin exhibits cytotoxic and immunosuppressive action, 9 causes inhibition of the syntheses of protein, DNA and RNA, 6,7 affects the cell cycle in human chondrocytes C28/12, hepatic epithelial L-02 and tubular epithelial HK-02 cells, 10 and induces apoptosis in fetal rat brain, 6 human chondrocytes, 11 different human cell lines, such as HeLa, Bel-7402, Chang liver cells, 12 human chondrocytes C28/12, hepatic epithelial L-02, and tubular epithelial HK-02 cells. 10 These studies indicate that T-2 toxin induces apoptosis through the reactive oxygen speciesmediated mitochondrial pathway by activating various signaling mediators, such as mitogen-activated protein kinases (MAPK) and caspases.…”

“…10 These studies indicate that T-2 toxin induces apoptosis through the reactive oxygen speciesmediated mitochondrial pathway by activating various signaling mediators, such as mitogen-activated protein kinases (MAPK) and caspases. 6,[10][11][12] European Food Safety Authority has established a tolerable daily intake (TDI) of 100 ng/kg body weight (bw) for the sum of T-2 and HT-2 toxins (the main metabolite of T-2 toxin) 13 and still has only recommendation values for their presence in cereals and cereal products within the European Union. 14 A number of studies have indicated adverse effects of T-2 toxin on reproduction and development in animals.…”

T-2 mycotoxin induced apoptosis in broiler’s liver tissue

“…fungus can induce apoptosis -a programmed cell death -of several cell lines of humans and animals [22]. Since T-2 toxin is a main type A trichothecene mycotoxin which is the most toxic trichothecence, it has posed various toxic effects on humans and animals in vigorous cell proliferation tissues like lymphoid, hematopoietic and gastrointestinal tissues [9,21].…”