Histone deacetylase inhibitors prevent H2O2 from inducing stress granule formation

Siyuan Feng, Jennifer Nichole Daw, Qin M. Chen

Research output: Contribution to journalArticlepeer-review

Abstract

Reactive Oxygen Species (ROS) are generated as by-products of aerobic metabolism. The production of ROS increases during xenobiotic stress and under multiple pathological conditions. Although ROS are considered harmful historically, mounting evidence recently indicates a signaling function of ROS, preceding to and regulating transcriptional or post-transcriptional events, contributing to cell death or cell survival and adaptation. Among the cellular defense mechanisms activated by ROS is formation of stress granules (SGs). The stalled translational apparatus, together with mRNA, aggregates into microscopically detectable and molecularly dynamic granules. We found that with H2O2, the dose most potent for inducing SGs in HeLa cells is 400–600 μM. With 200 μM H2O2, 2 h treatment induced the highest percentage of cells containing SGs. Whether ROS signaling pathways regulate the formation of SGs was tested using pharmacological inhibitors. We probed the potential role of PI3K, MAPKs, PKC or histone deacetylation in SG formation. Using deferoxamine as a positive control, we found a lack of inhibitory effect of wortmannin, LY-294002, JNK-I, SB-202190, PD-98059, or H89 when the percentage of cells containing SGs was counted. About 35% inhibition was observed with HDAC6 inhibitor Tubastatin A, whereas general HDAC inhibitor Trichostatin A provided a complete inhibition of SG formation. Our data point to the need of investigating the role of HDACs in SG formation during oxidative stress.

Original languageEnglish (US)
Pages (from-to)141-148
Number of pages8
JournalCurrent Research in Toxicology
Volume1
DOIs
StatePublished - Jun 10 2020

Keywords

  • Cytoprotection
  • Oxidative stress
  • Protein translation
  • Ribosomes
  • Signaling transduction

ASJC Scopus subject areas

  • Toxicology
  • Applied Microbiology and Biotechnology
  • Health, Toxicology and Mutagenesis

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