Role of estrogen receptor α and oxidative stress response proteins in the central nervous system

Cellular metabolism results in the production of reactive oxygen species (ROS) as byproducts and can damage proteins, lipids, and DNA. Cells utilize a number of enzymes and small molecules to scavenge ROS and prevent and repair damage that has occurred. To better understand the role three of these proteins play in responding to ROS, we examined the activity of Cu/Zn superoxide dismutase, apurinic endonuclease, and estrogen receptor α in the central nervous system. Our studies demonstrate that oxidative protein damage in the spinal cord occurred prior to the appearance of motor symptoms in mice that express a mutant form of Cu/Zn superoxide dismutase and subsequently develop symptoms of amyotrophic lateral sclerosis. Additionally, we show increased apurinic endonuclease expression in the cerebral cortex of mice that had been ovariectomized, treated with 17β-estradiol, and then exposed to hypoxia. A decline in oxidative DNA damage occurred which we believe was the result of the 17β-estradiol-mediated increase in apurinic endonuclease expression. Finally, our work shows that estrogen receptor α protein expression in the cerebral cortex was stable in aging, hormonally intact females and this estrogen receptor α protein was functional. Altogether, these studies demonstrate the importance of understanding the impact of ROS-induced damage on human health and disease and provide insight to develop methods of prevention and treatment for neurodegenerative disorders.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Molecular & Integrative Physi

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2014

Author dc:creator

• Dietrich, Alicia

Contributors dc:contributor

• Nardulli, Ann M.
• Katzenellenbogen, Benita S.
• Raetzman, Lori T.
• Roy, Edward J.

• Oxidative stress
• Estrogen receptor α
• Cu/Zn superoxide dismutase
• Amyotrophic lateral sclerosis
• Apurinic endonuclease 1
• Neuroprotection
• Hypoxia
• Estrogen

Statement dc:rights

• Copyright 2014 Alicia Dietrich

Language dc:language

en

Handle dc:identifier

http://hdl.handle.net/2142/50567

OAI record oai:identifier

https://www.ideals.illinois.edu/oai-pmh?verb=GetRecord&metadataPrefix=etdms&identifier=oai%3Awww.ideals.illinois.edu%3A2142%2F50567