HEI-OC1 听觉细胞和 H4 人类神经胶质瘤细胞继发于顺铂暴露的应激颗粒形成。

IF 4.1 Q2 CELL BIOLOGY
Cell Stress Pub Date : 2024-10-18 eCollection Date: 2024-01-01 DOI:10.15698/cst2024.10.299
Hebatallah Abdelrasol, Avika Chopra, Liana Shvachiy, Dirk Beutner, Tiago F Outeiro, Cristian Setz
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引用次数: 0

摘要

应激颗粒(SGs)是一种高度动态的无膜微分子凝聚体,在细胞受到应激时产生。应激颗粒由未翻译的信使核糖核蛋白(RNP)汇集而成,其动态变化对细胞的存活至关重要。在此,我们研究了铂类化疗药顺铂和氨基糖苷类抗生素庆大霉素等既有细胞毒性药物是否会诱发听觉细胞系House Ear Institute-Organ of Corti-1(HEI-OC1)、H4人类神经胶质瘤细胞和HEK-293T人类胚胎肾细胞中SG的形成。用指定浓度的顺铂或庆大霉素对细胞进行特定时间的处理。使用免疫细胞化学和活细胞成像技术评估 SG 的形成。使用免疫印迹法评估了参与 SG 组装的重要蛋白质的水平。我们通过共聚焦显微镜将 G3BP1 与 PABP 或 Caprin1 进行抗体标记,观察了 HEI-OC1 和 H4 细胞中与顺铂相关的 SG 组装。在保持主要组成 SG 蛋白表达模式不变的同时,H4 细胞中与顺铂相关的 SG 在去药后至少持续了 12 小时。暴露于庆大霉素的细胞没有出现 SG。我们的发现有助于深入了解与顺铂相关细胞毒性有关的亚细胞机制,并强调了今后进一步研究这种应激反应机制的必要性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Stress granules formation in HEI-OC1 auditory cells and in H4 human neuroglioma cells secondary to cisplatin exposure.

Stress granules (SGs) are highly dynamic micromolecular membraneless condensates that generate in cells subjected to stress. Formed from pools of untranslating messenger ribonucleoproteins (RNP), SGs dynamics constitute vital processes essential for cell survival. Here, we investigate whether established cytotoxic agents, such as the platinum-based chemotherapeutic agent cisplatin and the aminoglycoside antibiotic gentamicin, elicit SG formation in the House Ear Institute-Organ of Corti-1 (HEI-OC1) auditory cell line, H4 human neuroglioma cells and HEK-293T human embryonic kidney cells. Cells were treated with cisplatin or gentamicin for specific durations at designated concentrations. SG formation was assessed using immunocytochemistry and live cell imaging. Levels of essential proteins involved in SG assembly were evaluated using immunoblotting. We observed cisplatin-associated SG assembly in HEI-OC1 and H4 cells via confocal microscopy through antibody colabeling of G3BP1 with PABP or Caprin1. While maintaining an unchanged pattern of expression of main constituent SG proteins, cisplatin-related SGs in H4 cells persisted for at least 12 h after drug removal. Cells subjected to gentamicin exposure did not exhibit SGs. Our findings offer insights into subcellular mechanisms related to cisplatin-associated cytotoxicity, highlighting the need for future studies to further investigate this stress-response mechanism.

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来源期刊
Cell Stress
Cell Stress Biochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (miscellaneous)
CiteScore
13.50
自引率
0.00%
发文量
21
审稿时长
15 weeks
期刊介绍: Cell Stress is an open-access, peer-reviewed journal that is dedicated to publishing highly relevant research in the field of cellular pathology. The journal focuses on advancing our understanding of the molecular, mechanistic, phenotypic, and other critical aspects that underpin cellular dysfunction and disease. It specifically aims to foster cell biology research that is applicable to a range of significant human diseases, including neurodegenerative disorders, myopathies, mitochondriopathies, infectious diseases, cancer, and pathological aging. The scope of Cell Stress is broad, welcoming submissions that represent a spectrum of research from fundamental to translational and clinical studies. The journal is a valuable resource for scientists, educators, and policymakers worldwide, as well as for any individual with an interest in cellular pathology. It serves as a platform for the dissemination of research findings that are instrumental in the investigation, classification, diagnosis, and therapeutic management of major diseases. By being open-access, Cell Stress ensures that its content is freely available to a global audience, thereby promoting international scientific collaboration and accelerating the exchange of knowledge within the research community.
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