基于转录组学分析T-2毒素诱导细胞凋亡作用机制

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

摘要:

T-2毒素是一种强毒性单端孢霉烯族毒素，具有多器官效应毒性。为了解T-2毒素对不同细胞系毒性的影响及作用机制，作者分析了T-2毒素暴露对4种细胞系氧化应激、Ca²⁺水平和凋亡的影响，采用细胞转录组学等技术分析了T-2毒素作用于敏感细胞的关键基因和信号通路。结果表明，相同诱导剂量下，BV2小胶质细胞和HepG2肝癌细胞对T-2毒素敏感，细胞内活性氧（ROS）和Ca²⁺水平显著升高（P<0.05），细胞凋亡程度高。转录组学和逆转录-聚合酶链式反应（RT-PCR）结果显示，T-2毒素可通过MAPK/AP-1、TNF-NF-κB信号通路并上调AP-1、白细胞介素-6（IL-6）等因子水平引起BV2细胞炎症反应。而与氧化应激和凋亡相关的PI3K/AKT、PERK/P53/Casp3信号通路，通过下调Akt、SIRT1等促凋亡因子并上调超氧化物歧化酶促进了HepG2细胞的凋亡。T-2毒素分别通过促炎和氧化应激相关信号通路诱导BV2细胞和HepG2细胞凋亡，说明T-2毒素可通过不同的分子机制对不同器官产生特异性毒性效应。

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.