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

Dietrich, Alicia

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https://hdl.handle.net/2142/50567 Copy

Description

Title

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

Author(s)

Dietrich, Alicia

Issue Date

2014-09-16

Director of Research (if dissertation) or Advisor (if thesis)

Nardulli, Ann M.

Doctoral Committee Chair(s)

Nardulli, Ann M.

Committee Member(s)

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

Department of Study

Molecular & Integrative Physl

Discipline

Molecular & Integrative Physi

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

Ph.D.

Degree Level

Dissertation

Keyword(s)

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

Abstract

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.

Graduation Semester

2014-08

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

Copyright and License Information

Copyright 2014 Alicia Dietrich

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