國家衛生研究院 NHRI:Item 3990099045/9505

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Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/9505

Title:	The sigma-1 receptor-zinc finger protein 179 pathway protects against hydrogen peroxide-induced cell injury
Authors:	Su, TC;Lin, SH;Lee, PT;Yeh, SH;Hsieh, TH;Chou, SY;Su, TP;Hung, JJ;Chang, WC;Lee, YC;Chuang, JY
Contributors:	Institute of Biotechnology and Pharmaceutical Research
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.
Date:	2016-06
Relation:	Neuropharmacology. 2016 Jun;105:1-9.
Link to:	http://dx.doi.org/10.1016/j.neuropharm.2016.01.015
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0028-3908&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000377311300001
Cited Times(Scopus):	http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84954200165
Appears in Collections:	[Shiu-Hwa Yeh] Periodical Articles

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