Stress granules formation in HEI-OC1 auditory cells and in H4 human neuroglioma cells secondary to cisplatin exposure

Authors:

Hebatallah Abdelrasol1,a, Avika Chopra1,a, Liana Shvachiy1, Dirk Beutner2, Tiago F Outeiro1,3,4,5,* and Cristian Setz2,1,*
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Affiliations:

1 University Medical Center Göttingen, Department of Experimental Neurodegeneration, Center for Biostructural Imaging of Neurodegeneration, Göttingen, Germany. 2 University Medical Center Göttingen, Department of Otolaryngology-Head and Neck Surgery, Inner Ear Lab, Göttingen, Germany. 3 Max Plank Institute for Multidisciplinary Sciences, Göttingen, Germany. 4 Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom. 5 Scientific employee with an honorary contrat at Deutches Zentrum für Neurodegenerative Erkrankungen (DZNE)-German Center for Neurodegenerative Diseases, Göttingen, Germany.

Keywords: 

cisplatin, H4 cells, hearing loss, HEI-OC1 cells, ototoxicity, stress granules.

Abbreviations:

Caprin1 – cytoplasmic activation/proliferation-associated protein 1,

G3BP1 – Ras GTPase-activating protein-binding protein 1,

GFP – green fluorescence protein,

HEI-OC1 – House Ear Institute organ of Corti 1,

HEK – human embryonic kidney,

LLPS – liquid-liquid phase separation,

PABP – poly(A) binding protein,

RBP – RNA-binding protein,

RNP – ribonucleoprotein,

SG - stress granule,

TIA1 – T cell intracellular antigen 1.

Corresponding Author(s):

Cristian Setz, University Medical Center Göttingen, Department of Otolaryngology-Head and Neck Surgery, InnerEarLab, Göttingen, Germany; cristian.setz@med.uni-goettingen.de Tiago F Outeiro, University Medical Center Göttingen, Department of Otolaryngology-Head and Neck Surgery, InnerEarLab, Göttingen, Germany; tiago.outeiro@med.uni-goettingen.de

Conflict of interest statement:

The authors affirm that they have no conflicts of interest related to this work.

Please cite this article as:

Hebatallah Abdelrasol, Avika Chopra, Liana Shvachiy, Dirk Beutner, Tiago F Outeiro, Cristian Setz (2024). Stress granules formation in HEI-OC1 auditory cells and in H4 human neuroglioma cells secondary to cisplatin exposure. Cell Stress 8: 83-98. doi: 10.15698/cst2024.10.299

© 2024 Abdelrasol, Chopra et al. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.

Abstract:

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.