Glutathione S-transferase zeta 1 alters the HMGB1/GPX4 axis to drive ferroptosis in bladder cancer cells.

IF 2.7 4区医学 Q3 TOXICOLOGY Human & Experimental Toxicology Pub Date : 2023-01-01 DOI:10.1177/09603271231161606

Hongyan Zhu, Qitian Chen, Yang Zhang, Lingling Zhao

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引用次数: 2

Abstract

Objective: The ability of glutathione S-transferase zeta 1 (GSTZ1) to modulate homeostasis of cellular redox and induce ferroptosis was explored in bladder cancer cells, and the involvement of the high mobility group protein 1/glutathione peroxidase 4 (HMGB1/GPX4) in these effects was studied.

Methods: BIU-87 cells stably overexpressing GSTZ1 were transfected with appropriate plasmids to deplete HMGB1 or overexpress GPX4, then treated with deferoxamine and ferrostatin-1. Antiproliferative effects were assessed by quantifying levels of ferroptosis markers, such as iron, glutathione (GSH), malondialdehyde (MDA), reactive oxygen species (ROS), GPX4, transferrin, and ferritin.

Results: GSTZ1 was significantly downregulated in bladder cancer cells. GSTZ1 overexpression downregulated GPX4 and GSH, while greatly increasing levels of iron, MDA, ROS, and transferrin. GSTZ1 overexpression also decreased proliferation of BIU-87 cells and activated HMGB1/GPX4 signaling. The effects of GSTZ1 on ferroptosis and proliferation were antagonized by HMGB1 knockdown or GPX4 overexpression.

Conclusion: GSTZ1 induces ferroptotic cell death and alters cellular redox homeostasis in bladder cancer cells, and these effects involve activation of the HMGB1/GPX4 axis.

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谷胱甘肽s -转移酶zeta 1改变HMGB1/GPX4轴驱动膀胱癌细胞铁下垂。

目的:探讨谷胱甘肽s -转移酶zeta 1 (GSTZ1)调节膀胱癌细胞氧化还原稳态和诱导铁凋亡的能力，并研究高迁移率蛋白1/谷胱甘肽过氧化物酶4 (HMGB1/GPX4)在此过程中的作用。方法:用合适的质粒转染稳定过表达GSTZ1的BIU-87细胞，消耗HMGB1或过表达GPX4，然后用去铁胺和他铁素-1处理。通过定量铁坏死标志物(如铁、谷胱甘肽(GSH)、丙二醛(MDA)、活性氧(ROS)、GPX4、转铁蛋白和铁蛋白)的水平来评估抗增殖作用。结果:GSTZ1在膀胱癌细胞中表达显著下调。GSTZ1过表达下调GPX4和GSH，同时显著提高铁、MDA、ROS和转铁蛋白水平。GSTZ1过表达还能抑制BIU-87细胞的增殖，激活HMGB1/GPX4信号通路。GSTZ1抑制HMGB1或过表达GPX4可拮抗GSTZ1对铁下垂和增殖的影响。结论:GSTZ1诱导膀胱癌细胞凋亡并改变细胞氧化还原稳态，其作用可能与HMGB1/GPX4轴的激活有关。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Human & Experimental Toxicology 医学-毒理学

CiteScore

5.70

自引率

3.60%

发文量

128

审稿时长

2.3 months

期刊介绍： Human and Experimental Toxicology (HET), an international peer reviewed journal, is dedicated to publishing preclinical and clinical original research papers and in-depth reviews that comprehensively cover studies of functional, biochemical and structural disorders in toxicology. The principal aim of the HET is to publish timely high impact hypothesis driven scholarly work with an international scope. The journal publishes on: Structural, functional, biochemical, and molecular effects of toxic agents; Studies that address mechanisms/modes of toxicity; Safety evaluation of novel chemical, biotechnologically-derived products, and nanomaterials for human health assessment including statistical and mechanism-based approaches; Novel methods or approaches to research on animal and human tissues (medical and veterinary patients) investigating functional, biochemical and structural disorder; in vitro techniques, particularly those supporting alternative methods