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

Neuropharmacology
Tzu-Chieh SuJian-Ying Chuang

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, t...Continue Reading

References

Apr 25, 1995·Proceedings of the National Academy of Sciences of the United States of America·F P MonnetE E Baulieu
May 29, 2003·Current Drug Targets. CNS and Neurological Disorders·Vincenzo Di Matteo, Ennio Esposito
May 19, 2004·Proceedings of the National Academy of Sciences of the United States of America·Ioannis CharalampopoulosAchille Gravanis
Aug 19, 2007·Nature Reviews. Molecular Cell Biology·Marco GiorgioPier Giuseppe Pelicci
Mar 29, 2008·Current Neuropharmacology·T Hayashi, Tp Su
Apr 14, 2011·The Journal of Physiology·João Paulo Gabriel CamporezCarla Roberta de Oliveira Carvalho
Oct 30, 2012·Trends in Neurosciences·Saïd KourrichAntonello Bonci
Jan 19, 2013·Nature Reviews. Neuroscience·Ye XiongMichael Chopp
Dec 20, 2013·Current Medicinal Chemistry·Ana Rodríguez-RodríguezAntonio Carrillo-Vico
Mar 13, 2014·Nature Reviews. Neuroscience·Claudio Hetz, Bertrand Mollereau
Apr 2, 2014·BioMed Research International·André Mendes ArentAlcir Luiz Dafre
Feb 18, 2015·Progress in Neuro-psychopharmacology & Biological Psychiatry·Diana M F HannaAmani E Khalifa
Feb 24, 2015·Journal of Pharmacological Sciences·Linda NguyenRae R Matsumoto
Feb 24, 2015·Journal of Pharmacological Sciences·Karsten Ruscher, Tadeusz Wieloch
Nov 11, 2015·Proceedings of the National Academy of Sciences of the United States of America·Shang-Yi A TsaiTsung-Ping Su

❮ Previous
Next ❯

Citations

Feb 8, 2019·Journal of Basic and Clinical Physiology and Pharmacology·Junaidi KhotibUNKNOWN Suharjono
Sep 18, 2017·Journal of Biomedical Science·Tzu-Yu WengTsung-Ping Su
Aug 8, 2019·Trends in Pharmacological Sciences·Hayden R Schmidt, Andrew C Kruse
Dec 19, 2020·Biochemical and Biophysical Research Communications·Chu-Jen KuoYi-Chao Lee

❮ Previous
Next ❯

Related Concepts

Related Feeds

Bioinformatics in Biomedicine

Bioinformatics in biomedicine incorporates computer science, biology, chemistry, medicine, mathematics and statistics. Discover the latest research on bioinformatics in biomedicine here.

Brain Injury & Trauma

brain injury after impact to the head is due to both immediate mechanical effects and delayed responses of neural tissues.

Anti-inflammatory Treatments

A drug or substance that reduces inflammation (redness, swelling, and pain) in the body. Anti-inflammatory agents block certain substances in the body that cause inflammation and swelling. Discover the latest research on anti-inflammatory treatments here

Astrocytes

Astrocytes are glial cells that support the blood-brain barrier, facilitate neurotransmission, provide nutrients to neurons, and help repair damaged nervous tissues. Here is the latest research.

Astrocytes & Neurodegeneration

Astrocytes are important for the health and function of the central nervous system. When these cells stop functioning properly, either through gain of function or loss of homeostatic controls, neurodegenerative diseases can occur. Here is the latest research on astrocytes and neurodegeneration.

Astrocytes in Repair & Regeneration

Astrocytes are glial cells found within the CNS and are able to regenerate new neurons. They become activated during CNS injury and disease. The activation leads to the transcription of new genes and the repair and regeneration of neurons. Discover the latest research on astrocytes in repair and regeneration here.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis