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Katzenellenbogen, Benita S. Nardulli, Ann M. Rao, Abhilasha 2014-12-17T22:58:20Z 2014-12-17T22:58:20Z 10000-01-01 2009 2009 The classical genomic pathway for 17beta-estradiol (E 2) action involves binding to estrogen receptor alpha (ERalpha) in target cells, interaction with estrogen response element (ERE)-containing DNA, recruitment of coregulatory proteins, and modification of estrogen responsive genes. Because DNA-induced conformational changes in ERalpha structure alter complex formation, we were interested in identifying proteins associated with the ERE-bound receptor. Using a novel electrophoretic fractionation method, we identified a number of proteins involved in oxidative stress response including Cu/Zn superoxide dismutase (SOD1), thioredoxin (Trx) and thioredoxin reductase (TrxR). We found that SOD1 interacts with ERalpha, enhances ERalpha-ERE complex formation, influences estrogen responsiveness and associates with estrogen responsive regions of the pS2 and progesterone receptor genes. Furthermore, when MCF-7 breast cancer cells are exposed to E2 and superoxide SOD1 levels increase and oxidative stress-induced protein damage is greatly reduced. We also demonstrate that endogenously-expressed ERalpha, Trx, and TrxR interact, differentially influence endogenous estrogen-responsive gene expression, and alter hydrogen peroxide levels in MCF-7 cells. Additional characterization using brain slice cultures suggests a protective role for E2 and SOD1 in the cerebral cortex. These combined studies highlight a novel link between oxidative stress proteins and ERalpha-mediated gene expression in target tissues. Made available in DSpace on 2014-12-17T22:58:20Z (GMT). No. of bitstreams: 1 3392443.pdf: 1153354 bytes, checksum: 173961dc240994ea03cf395110b6e1f1 (MD5) Previous issue date: 2009 Embargo set by: Seth Robbins for item 72656 Lift date: Forever Reason: Restricted to the U of I community idenfinitely during batch ingest of legacy ETDs Restricted to the U of I community idenfinitely during batch ingest of legacy ETDs U of I Only 68 p. Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 2009. http://hdl.handle.net/2142/72488 (UMI)AAI3392443 Biology, Molecular Biology, Physiology A Novel Link Between Oxidative Stress Proteins and Estrogen Receptor Alpha-Mediated Gene Expression text Cell and Developmental Biology Cell and Developmental Biology University of Illinois at Urbana-Champaign Dissertation Ph.D.