{"title":"Tert-butyl hydroperoxide induces trabecular meshwork cells injury through ferroptotic cell death","authors":"Xuejing Yan, Qian Liu, Shen Wu, Xiaowei Fan, Yufei Teng, Ningli Wang, Jingxue Zhang","doi":"10.1002/ccs3.12050","DOIUrl":null,"url":null,"abstract":"<p>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.</p>","PeriodicalId":15226,"journal":{"name":"Journal of Cell Communication and Signaling","volume":null,"pages":null},"PeriodicalIF":3.6000,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ccs3.12050","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Cell Communication and Signaling","FirstCategoryId":"99","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/ccs3.12050","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0
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.
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.