Treatment with paraquat affects the expression of ferroptosis-related genes

Author:

Ge Xiaogang1,Cai Qiqi2ORCID,Zhang Sheng2,Wu Xianlong2,Ying Pan2,Ke Jingjing2,Yang Zhihui2

Affiliation:

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

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

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— Chac1 (ChaC glutathione specific gamma-glutamylcyclotransferase 1), Atf3 (activating transcription factor 3), Tfrc (transferrin receptor), and Slc7a11 (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.

Funder

Health Science and Technology Project of Zhejiang Province

Taizhou Science and Technology Department Project

Publisher

SAGE Publications

Subject

Health, Toxicology and Mutagenesis,Toxicology,General Medicine

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