Mechanism of T-2 Toxin Induction in Promoting Cell Apoptosis Based on Transcriptomics

Abstract:

T-2 toxin is a highly toxic trichothecene compound, which exhibits multi-organ toxicity. To investigate the toxic effects of T-2 toxin on different cell lines and the related molecular mechanisms, we analyzed the effects of T-2 toxin exposure on oxidative stress, Ca²⁺ levels, and apoptosis in four cell lines. The key genes and potential signaling pathways of T-2 toxin on sensitive cells were analyzed using transcriptomics. Results revealed that BV2 microglial cells and HepG2 cells exhibited sensitivity to T-2 toxin, displaying a significant increase in intracellular reactive oxygen species (ROS) and Ca²⁺ levels, leading to elevated cell apoptosis. Transcriptomic data and RT-PCR analysis indicated that T-2 toxin triggered apoptosis in BV2 and HepG2 cells through distinct signaling pathways. Additionally, BV2 cells showed an inflammatory response via the MAPK/AP-1 and TNF-NF-κB pathways, upregulating factors like AP-1 and IL-6. Conversely, HepG2 cells underwent apoptosis through the PI3K/AKT and PERK/P53/Casp3 pathways, downregulating Akt and SIRT1, while upregulating superoxide dismutase. Overall, T-2 toxin induced apoptosis in BV2 and HepG2 cells, respectively through inflammatory and oxidative stress-related pathways, highlighting its potential to affect different organs via diverse molecular mechanisms.