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

作　　者：叶永丽 高露 纪剑 孙嘉笛 王加生[3] 张银志[1] 孙秀兰[1,2] YE Yongli;GAO Lu;JI Jian;SUN Jiadi;WANG Jiasheng;ZHANG Yinzhi;SUN Xiulan(School of Food Science and Technology,Jiangnan University,Wuxi 214122,China;State Administration for Market Regulation(Key Laboratory of Screening,Prevention,and Control of Food Safety Risks),Beijing 100176,China;College of Public Health,University of Georgia,Athens 30602,USA)

机构地区：[1]江南大学食品学院,江苏无锡214122 [2]国家市场监督管理总局重点实验室(食品安全风险物质甄别与防控),北京100176 [3]美国佐治亚大学公共卫生学院,佐治亚雅典30602

出　　处：《食品与生物技术学报》2024年第7期56-66,共11页Journal of Food Science and Biotechnology

基　　金：国家“十四五”重点研发计划项目(2022YFE0137500)。

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、Ca^(2+)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Ca^(2+)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。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,Ca^(2+)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 Ca^(2+)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 stressrelated pathways,highlighting its potential to affect different organs via diverse molecular mechanisms.

关 键 词：T-2毒素 细胞毒性 转录组学 氧化应激 炎症反应 

分 类 号：TS201.6[轻工技术与工程—食品科学]