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呕吐毒素致HK2细胞氧化应激的作用机制

Mechanism for Vomitoxin-induced Oxidative Stress in HK2 Cells
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摘要 该文探究了呕吐毒素(Deoxynivalenol,DON)对人肾小管上皮细胞(Humankideny-2,HK2)氧化应激的作用机制。通过MTT法测定DON的细胞毒性,Western blotting检测细胞凋亡蛋白Bax、Bcl-2、Caspase-2、Caspase-3、Caspase-6、Caspase-8和Caspase-9的表达水平。利用转录组测序技术(RNA-seq)研究了DON染毒24 h诱导的HK2细胞基因组表达情况,并进行差异表达基因GO与KEGG富集分析。结果表明,DON使HK2细胞LDH、MDA和ROS水平上升,SOD和GSH等抗氧化指标下降;IL-6、IL-1β和TNF-α等炎症指标升高。Bax和caspase蛋白表达上调,Bcl-2蛋白表达下调。转录组测序表明,40μmol/L DON诱导的差异表达基因共有5962个,其中上调表达的基因有2813个,下调表达的基因有3149个。综上所述,蛋白水平与基因谱表达趋势一致,DON对HK2细胞具有毒性作用,诱导HK2细胞氧化应激,通过Caspase、MAPK和PI3K-Akt等信号通路影响肾功能与代谢,为DON肾毒性作用和相关机制的调控提供理论依据。 The mechanism of action of deoxynivalenol(DON)on oxidative stress in human renal tubular epithelial cells(Human Kidney-2,HK2)was explored in this article.DON cytotoxicity was assessed using the MTT assay,and the expression levels of apoptosis-regulating proteins-including Bax,Bcl-2,Caspase-2,Caspase-3,Caspase-6,Caspase-8,and Caspase-9-was measured by Western blotting.Transcriptome sequencing(RNA-seq)analyzed the genome-wide expression profile of HK2 cells following 24-hour DON exposure.DON exposure elevated LDH,MDA,and ROS levels in HK2 cells,while reducing antioxidant indicators such as SOD and GSH and increasing inflammatory markers IL-6,IL-1β,and TNF-α.Bax and caspase protein expressions were upregulated,while Bcl-2 protein expression was downregulated.Transcriptome analysis identified 5962 differentially expressed genes after exposure to 40μmol/L DON,with 2813 upregulated and 3149 downregulated.Protein levels aligned with gene expression profiles.DON induces oxidative stress and nephrotoxicity in HK2 cells,affecting renal function and metabolism through signaling pathways,including Caspase,MAPK,and PI3K-Akt.These findings offer a theoretical basis for the regulation of DON-induced nephrotoxicity.
作者 焦禄 张百刚 李苏冰 李阳 付炳钢 JIAO Lu;ZHANG Baigang;LI Subing;LI Yang;FU Binggang(School of Life Science and Engineering,Lanzhou University of Technology,Lanzhou 730050,China)
出处 《现代食品科技》 北大核心 2025年第1期8-16,共9页 Modern Food Science and Technology
基金 国家自然科学基金项目(31760495) 甘肃省自然科学基金项目(18JR3RA136)。
关键词 呕吐毒素 氧化胁迫 炎症反应 细胞凋亡 差异基因分析 vomitoxin oxidative stress inflammatory reactions apoptosis differential gene analysis
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