百草枯治疗会影响铁死亡相关基因的表达。

Treatment with paraquat affects the expression of ferroptosis-related genes.

机构信息

Vascular and Endovascular Surgery, 618847Huangyan Hospital Affiliated to Wenzhou Medical University, Taizhou, China.

Department of Emergency Intensive Care Unit, 618847Huangyan Hospital Affiliated to Wenzhou Medical University, Taizhou, China.

出版信息

Hum Exp Toxicol. 2023 Jan-Dec;42:9603271231167585. doi: 10.1177/09603271231167585.

DOI:10.1177/09603271231167585

PMID:36960817

Abstract

OBJECTIVE

We aimed to explore the mechanisms underlying paraquat (PQ)-induced damage using cell lines (NCTC1469, TC-1, TCMK-1) and bioinformatic analysis of the GSE153959 dataset. Assessment of changes in the expression of ferroptosis-related genes in cellular damage due to paraquat poisoning and the important value of these genes in the pathogenesis.

METHODS

Data were retrieved from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) related to ferroptosis were identified by Venn plots and analyzed for enrichment. Proteins encoded by these DEGs were studied for interactions. qRT-PCR and western blotting analyses of cultured cells were used to determine the expression of ferroptosis-related DEGs and their corresponding protein levels.

RESULTS

We identified 25 DEGs primarily involved in epidermal growth factor receptor signaling, apoptotic signaling pathways, endoplasmic reticulum (ER) stress, and ferroptosis. From these, we uncovered eight ferroptosis-related DEGs, four of which were involved in ER response and regulators of ferroptosis- (ChaC glutathione specific gamma-glutamylcyclotransferase 1), (activating transcription factor 3), (transferrin receptor), and (solute carrier family 7 member 11). Significant changes in mRNA and protein levels of CHAC1, ATF3, TFRC, and SLC7A11 were confirmed in PQ-exposed cells.

CONCLUSION

ER stress and ferroptosis are critical for PQ-induced cell damage. CHAC1, ATF3, TFRC, and SLC7A11 are essential molecules implicated in PQ-induced ferroptosis that may serve as therapeutic targets for the amelioration of PQ poisoning.

摘要

目的

本研究旨在通过细胞系（NCTC1469、TC-1、TCMK-1）和对 GSE153959 数据集的生物信息学分析，探讨百草枯（PQ）诱导损伤的机制。评估 PQ 中毒导致细胞损伤中与铁死亡相关基因的表达变化及其在发病机制中的重要价值。

方法

从基因表达综合数据库中检索数据。通过 Venn 图识别与铁死亡相关的差异表达基因（DEGs），并进行富集分析。研究这些 DEGs 编码的蛋白质之间的相互作用。采用 qRT-PCR 和 Western blot 分析培养细胞，以确定铁死亡相关 DEGs 的表达及其相应蛋白水平。

结果

我们确定了 25 个主要涉及表皮生长因子受体信号、凋亡信号通路、内质网（ER）应激和铁死亡的 DEGs。从中，我们发现了 8 个与铁死亡相关的 DEGs，其中 4 个与 ER 反应和铁死亡调节剂有关（谷氨酰半胱氨酸特异性γ-谷氨酰环转移酶 1）、（激活转录因子 3）、（转铁蛋白受体）和（溶质载体家族 7 成员 11）。在 PQ 暴露的细胞中，CHAC1、ATF3、TFRC 和 SLC7A11 的 mRNA 和蛋白水平均发生显著变化。