The sigma-1 receptor-zinc finger protein 179 pathway protects against hydrogen peroxide-induced cell injury

Tzu Chieh Su, Shu Hui Lin, Pin Tse Lee, Shiu Hwa Yeh, Tsung Hsun Hsieh, Szu Yi Chou, Tsung Ping Su, Jan Jong Hung, Wen Chang Chang, Yi Chao Lee, Jian Ying Chuang

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Abstract

The accumulation of reactive oxygen species (ROS) have implicated the pathogenesis of several human diseases including neurodegenerative disorders, stroke, and traumatic brain injury, hence protecting neurons against ROS is very important. In this study, we focused on sigma-1 receptor (Sig-1R), a chaperone at endoplasmic reticulum, and investigated its protective functions. Using hydrogen peroxide (H2O2)-induced ROS accumulation model, we verified that apoptosis-signaling pathways were elicited by H2O2 treatment. However, the Sig-1R agonists, dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS), reduced the activation of apoptotic pathways significantly. By performing protein-protein interaction assays and shRNA knockdown of Sig-1R, we identified the brain Zinc finger protein 179 (Znf179) as a downstream target of Sig-1R regulation. The neuroprotective effect of Znf179 overexpression was similar to that of DHEAS treatment, and likely mediated by affecting the levels of antioxidant enzymes. We also quantified the levels of peroxiredoxin 3 (Prx3) and superoxide dismutase 2 (SOD2) in the hippocampi of wild-type and Znf179 knockout mice, and found both enzymes to be reduced in the knockout versus the wild-type mice. In summary, these results reveal that Znf179 plays a novel role in neuroprotection, and Sig-1R agonists may be therapeutic candidates to prevent ROS-induced damage in neurodegenerative and neurotraumatic diseases.

Original languageEnglish
Pages (from-to)1-9
Number of pages9
JournalNeuropharmacology
Volume105
DOIs
Publication statusPublished - 2016 Jun

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Cellular and Molecular Neuroscience

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    Su, T. C., Lin, S. H., Lee, P. T., Yeh, S. H., Hsieh, T. H., Chou, S. Y., Su, T. P., Hung, J. J., Chang, W. C., Lee, Y. C., & Chuang, J. Y. (2016). The sigma-1 receptor-zinc finger protein 179 pathway protects against hydrogen peroxide-induced cell injury. Neuropharmacology, 105, 1-9. https://doi.org/10.1016/j.neuropharm.2016.01.015