T-2 Toxin Induces Apoptotic Cell Death and Protective Autophagy in Mouse Microglia BV2 Cells

Abstract

T-2 toxin exposure could cause neurotoxicity; however, the precise molecular mechanisms remain unclear. In the present study, we investigated T-2 toxin-induced cytotoxicity and underlying molecular mechanisms using a mouse microglia BV2 cell line. The results show that T-2 toxin treatment-induced cytotoxicity of BV2 cells was dose- and time-dependent. Compared to the control, T-2 toxin treatment at 1.25–5 ng/mL significantly increased reactive oxygen species (ROS) production and triggered oxidative stress. T-2 toxin treatment also caused mitochondrial dysfunction in BV2 cells, which was evidenced by decreased mitochondrial transmembrane potential, upregulated expression of Bax protein, and decreased expression of Bcl-2 protein. Meanwhile, T-2 toxin treatment upregulated the expression of cleaved-caspase-3, cleaved-PARP-1 proteins, and downregulated the expression of HO-1 and nuclear Nrf2 proteins, finally inducing cell apoptosis in BV2 cells. N-acetylcysteine (NAC) supplementation significantly attenuated T-2 toxin-induced cytotoxicity. Moreover, T-2 toxin treatment activated autophagy and upregulated autophagy flux, and the inhibition of autophagy significantly promoted T-2 toxin-induced cell apoptosis. Taken together, our results reveal that T-2 toxin-induced cytotoxicity in BV2 cells involves the production of ROS, the activation of the mitochondrial apoptotic pathway, and the inhibition of the Nrf2/HO-1 pathway. Our study offers new insight into the underlying molecular mechanisms in T-2 toxin-mediated neurotoxicity.

Chelerythrine-Induced Apoptotic Cell Death in HepG2 Cells Involves the Inhibition of Akt Pathway and the Activation of Oxidative Stress and Mitochondrial Apoptotic Pathway

“…Oxidative stress could be induced by the imbalance between the production of intracellular ROS and antioxidant systems and it plays a critical role in the process of cytotoxicity caused by various exogenous compounds, such as mycotoxins (e.g., T-2 toxin), heavy metals (e.g., copper), or drugs (e.g., quinocetone, colistin, and furazolidone) [ 26 , 27 , 34 , 35 , 36 ]. It is well known that intracellular ROS contains the superoxide anion (O 2 •− ), hydroxyl radicals (OH·), and hydrogen peroxide (H 2 O 2 ) [ 37 ].…”

Differential Role of Active Compounds in Mitophagy and Related Neurodegenerative Diseases

“…This toxin can be found in crops of corn, wheat, barley, and rice in the field, during storage or in drinking water—in particular, it was found in a number of provinces in China [ 118 ]. T-2 toxin can be easily absorbed through the intestines and penetrate the blood–brain barrier, lung mucosa, and skin system, damaging the skin, kidneys, liver, brain, heart, spleen, hematopoietic system, lymphoid system of the gastrointestinal tract, bone marrow, and reproductive system [ 78 ]. Neurotoxicity caused by T-2 toxin is associated with the production of ROS, oxidative stress, mitochondrial dysfunction, cell cycle arrest, DNA damage, and inflammatory responses [ 76 , 77 ].…”

“…During the experiments, it was possible to determine that T-2 toxin causes neurotoxic effects, as well as induces a loss of mitochondrial membrane potential in BV2 microglial cells. Exposure to T-2 toxin activates autophagy in the cell, and this autophagy plays a protective role, accompanied by increased expression of Beclin1 and LC3II proteins [ 78 ]. Yet, to date, there are no published articles on the role of T-2 toxin in relation to mitophagy in neurons or astrocytes (see Table 1 ).…”

Effective protective agents against the organ toxicity of T-2 toxin and corresponding detoxification mechanisms: A narrative review

“… Preventing ROS production and mitochondrial dysfunction; Reducing mitochondrial transmembrane potential. Sun et al. (2022) BA Mice Pretreated with BA (0.25, 0.5, and 1.00 mg/kg BW) for 14 d; T-2 (4 mg/kg BW, single i.p.).…”