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

Content Provider	Scilit
Author	Su, Tzu-Chieh Lin, Shu-Hui Lee, Pin-Tse Yeh, Shiu-Hwa Hsieh, Tsung-Hsun Chou, Szu-Yi Su, Tsung-Ping Hung, Jan-Jong Chang, Wen-Chang Lee, Yi-Chao Chuang, Jian-Ying
Copyright Year	2016
Description	Journal: Neuropharmacology 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 $(H_{2}O_{2}$)-induced ROS accumulation model, we verified that apoptosis-signaling pathways were elicited by $H_{2}O_{2}$ 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.
Related Links	http://europepmc.org/articles/pmc5520630?pdf=render https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5520630/pdf
Ending Page	9
Page Count	9
Starting Page	1
ISSN	00283908
e-ISSN	18737064
DOI	10.1016/j.neuropharm.2016.01.015
Journal	Neuropharmacology
Volume Number	105
Language	English
Publisher	Elsevier BV
Publisher Date	2016-01-11
Access Restriction	Open
Subject Keyword	Journal: Neuropharmacology Biochemistry and Molecular Biology Reactive Oxygen Species Hydrogen Peroxide
Content Type	Text
Resource Type	Article
Subject	Pharmacology Cellular and Molecular Neuroscience