Tert-butyl hydroperoxide induces trabecular meshwork cells injury through ferroptotic cell death

IF 3.6 3区 生物学 Q3 CELL BIOLOGY Journal of Cell Communication and Signaling Pub Date : 2024-08-28 DOI:10.1002/ccs3.12050
Xuejing Yan, Qian Liu, Shen Wu, Xiaowei Fan, Yufei Teng, Ningli Wang, Jingxue Zhang
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Abstract

Trabecular meshwork (TM) tissue has a crucial role in regulating aqueous humor circulation in the eye, thus maintaining normal intraocular pressure (IOP). TM dysfunction causes IOP elevation, which leads to glaucoma. To investigate biological changes in TM tissue in patients with glaucoma, we analyzed the mRNA expression microarray dataset, GSE27276. Gene ontology analysis indicated that redox microenvironment imbalance is among the main changes of TM tissue in patients with glaucoma. Subsequently, we induced oxidative stress in TM cells using the tert-butyl hydroperoxide (tBHP) treatment, to generate in vivo and in vitro models, and conducted mRNA sequencing to identify genes with critical roles in maintaining the redox microenvironment balance. We found that the tBHP caused TM dysfunction in vivo, characterized by aqueous humor circulation resistance, IOP elevation, and TM cell death. Further, Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that ferroptosis signaling was enriched in tBHP-treated TM cells. Consistently, in vitro analyses showed that levels of reactive oxygen species, ferric ion, and malondialdehyde were increased after the tBHP treatment, indicating TM cell ferroptosis. Furthermore, inhibiting ferroptosis alleviated tBHP-induced TM cell injury. This study provides new insights suggesting that inhibition of ferroptosis has potential as a treatment for glaucoma.

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叔丁基过氧化氢通过铁性细胞死亡诱导小梁网细胞损伤
小梁网(TM)组织在调节眼内房水循环,从而维持正常眼压(IOP)方面起着至关重要的作用。小梁网功能障碍会导致眼压升高,从而引发青光眼。为了研究青光眼患者 TM 组织的生物学变化,我们分析了 mRNA 表达微阵列数据集 GSE27276。基因本体分析表明,氧化还原微环境失衡是青光眼患者 TM 组织的主要变化之一。随后,我们利用叔丁基过氧化氢(tBHP)处理诱导TM细胞氧化应激,生成体内和体外模型,并进行mRNA测序以鉴定在维持氧化还原微环境平衡中起关键作用的基因。我们发现,tBHP 会导致体内 TM 功能障碍,表现为房水循环阻力、眼压升高和 TM 细胞死亡。此外,京都基因和基因组百科全书的通路分析表明,在经 tBHP 处理的 TM 细胞中,富含铁突变信号。体外分析表明,经 tBHP 处理后,活性氧、铁离子和丙二醛的水平升高,这表明 TM 细胞发生了铁变态反应。此外,抑制铁变态反应可减轻 tBHP 引起的 TM 细胞损伤。这项研究提供了新的见解,表明抑制铁突变具有治疗青光眼的潜力。
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来源期刊
CiteScore
6.40
自引率
4.90%
发文量
40
期刊介绍: The Journal of Cell Communication and Signaling provides a forum for fundamental and translational research. In particular, it publishes papers discussing intercellular and intracellular signaling pathways that are particularly important to understand how cells interact with each other and with the surrounding environment, and how cellular behavior contributes to pathological states. JCCS encourages the submission of research manuscripts, timely reviews and short commentaries discussing recent publications, key developments and controversies. Research manuscripts can be published under two different sections : In the Pathology and Translational Research Section (Section Editor Andrew Leask) , manuscripts report original research dealing with celllular aspects of normal and pathological signaling and communication, with a particular interest in translational research. In the Molecular Signaling Section (Section Editor Satoshi Kubota) manuscripts report original signaling research performed at molecular levels with a particular interest in the functions of intracellular and membrane components involved in cell signaling.
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