Abstract
T-2 toxin, as a highly toxic mycotoxin to humans and animals, induces oxidative stress and apoptosis in various cells and tissues. Apoptosis and mitochondrial fusion/fission are two tightly interconnected processes that are crucial for maintaining physiological homeostasis. However, the role of mitochondrial fusion/fission in apoptosis of T-2 toxin remains unknown. Hence, we aimed to explore the putative role of mitochondrial fusion/fission on T-2 toxin induced apoptosis in normal human liver (HL-7702) cells. T-2 toxin treatment (0, 0.1, 1.0, or 10 μg/L) for 24 h caused decreased cell viability and ATP concentration and increased production of (ROS), as seen by a loss of mitochondrial membrane potential (∆Ψm) and increase in mitochondrial fragmentation. Subsequently, the mitochondrial dynamic imbalance was activated, evidenced by a dose-dependent decrease and increase in the protein expression of mitochondrial fusion (OPA1, Mfn1, and Mfn2) and fission (Drp1 and Fis1), respectively. Furthermore, the T-2 toxin promoted the release of cytochrome c from mitochondria to cytoplasm and induced cell apoptosis triggered by upregulation of Bax and Bax/Bcl-2 ratios, and further activated the caspase pathways. Taken together, these results indicate that altered mitochondrial dynamics induced by oxidative stress with T-2 toxin exposure likely contribute to mitochondrial injury and HL-7702 cell apoptosis.
Highlights
T-2 toxin, a fungal secondary metabolite that belongs to the type A trichothecene mycotoxin family, is produced by various Fusarium species [1]
Some recent reports indicated that mitochondrial toxicity is another major adverse effect of T-2 toxin, characterized by inhibition of enzymatic activity of mitochondrial respiratory chain (MRC) complexes, collapse of ∆Ψm, opening of the mitochondrial permeability transition pore (MPTP), decrease in intracellular adenosine triphosphate (ATP) contents, and increase in the level of reactive oxygen species (ROS), which could activate proapoptotic members of the B-cell lymphoma 2 (Bcl-2) family such as Bax and Bak, and subsequently trigger abnormal caspase-3 activity and apoptosis in different cell lines [11,13,14]
These results show that a T-2 toxin triggers oxidative stress and interrupts the dynamic balance between mitochondrial fusion and fission, with this equilibrium being essential for a wide range of biological processes
Summary
T-2 toxin, a fungal secondary metabolite that belongs to the type A trichothecene mycotoxin family, is produced by various Fusarium species [1]. As one of the most toxic trichothecene mycotoxins, T-2 toxin can cause serious toxicosis in humans and farm animals via ingestion of contaminated food and feed [3]. There is growing evidence to show that T-2 toxins could impair immunological functions; inhibit protein and DNA synthesis; promote oxidative stress; disturb. Some recent reports indicated that mitochondrial toxicity is another major adverse effect of T-2 toxin, characterized by inhibition of enzymatic activity of mitochondrial respiratory chain (MRC) complexes, collapse of ∆Ψm, opening of the mitochondrial permeability transition pore (MPTP), decrease in intracellular adenosine triphosphate (ATP) contents, and increase in the level of reactive oxygen species (ROS), which could activate proapoptotic members of the B-cell lymphoma 2
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