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Updated: May 8, 2025
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Methods to Classify Cytoplasmic Foci as Mammalian Stress Granules
Published on: May 12, 2017
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Intracellular hydrogen sulfide induces stress granule formation and translational repression through eIF2α
S Kanno1, S Hirano2, J Monma-Otaki3
1Department of Forensic Medicine, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan. sanae@med.nagoya-cu.ac.jp.
Archives of Toxicology
|April 9, 2025
Summary
High concentrations of hydrogen sulfide (H2S) trigger stress granule formation in lung cells, a protective response involving eIF2α phosphorylation. This process limits protein synthesis to mitigate H2S-induced cell damage.
Area of Science:
- Cell Biology
- Toxicology
- Molecular Biology
Background:
- Hydrogen sulfide (H2S) is a toxic gas causing severe respiratory damage.
- Stress granules (SGs) are cellular structures that form under stress to protect cells.
- Understanding H2S toxicity mechanisms is crucial for respiratory health.
Purpose of the Study:
- To investigate stress granule (SG) formation in response to high H2S concentrations.
- To elucidate the molecular pathways involved in H2S-induced SG formation.
- To determine the role of specific cellular components in H2S toxicity.
Main Methods:
- Exposure of human bronchial BEAS-2B and CHO cells to varying concentrations of NaHS (H2S source).
- Microscopic analysis for SG formation and intracellular H2S levels.
- Pharmacological inhibition/enhancement of key signaling pathways (PERK, eIF2α, GSH, Trx).
Main Results:
- Intracellular H2S levels increased dose-dependently after NaHS exposure.
- Discrete SG assemblies formed rapidly in both cell lines within 1 hour.
- SG formation was modulated by inhibitors/enhancers of GSH, Trx, PERK, and the integrated stress response.
- eIF2α phosphorylation significantly increased, correlating with SG formation and reduced protein synthesis.
Conclusions:
- H2S exposure induces SG formation and translational repression via eIF2α phosphorylation in pulmonary cells.
- Glutathione (GSH) and thioredoxin (Trx) appear to play protective roles in mitigating H2S-induced SG formation.
- The PERK pathway is partially involved in H2S-induced SG formation, contributing to cell protection against H2S toxicity.
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