Theses and Dissertations
Permanent URI for this collectionhttps://hdl.handle.net/20.500.12503/21598
Browse
Browsing Theses and Dissertations by Subject "17-beta estradiol"
Now showing 1 - 2 of 2
- Results Per Page
- Sort Options
Item Modulation of Manganese Superoxide Dismutase by 17-Beta Estradiol(2008-05-01) Gottipati, Srinivas; Thomas YorioGottipati, Srinivas. Modulation of manganese superoxide dismutase activity by 17-beta estradiol. Master of Science (Cell Biology and Genetics), May, 2008. We have previously reported that 17β-Estradiol (17β-E2) can protect human lens epithelial cells against oxidative stress by preserving mitochondrial function, acting as a positive regulator of the MAPK signal transduction pathway. While pERK plays a significant role in stabilizing the inner mitochondrial membrane to maintain the mitochondrial membrane potential during oxidative stress, the protective mechanisms activated by 17β-E2 are probably multifactorial acting via both genomic and non genomic pathways. This study examined the effects of 17β-E2 on the expression and activity of MnSOD, which is present exclusively in the mitochondria, as a possible mechanism by which it affords protection against oxidative stress. Our results demonstrate that 17β-E2 rapidly increases the activity of MnSOD in a time dependent manner. This augmentation of activity of MnSOD by 17β-E2 is seen in the absence of a corresponding increase in the mRNA and protein expression, thereby which estrogens protect the cells against oxidative stress will help us in developing estrogens to be useful therapies for the prevention of cataract in postmenopausal women and non feminizing estrogens may provide similar protection in men.Item Translational Control by Estrogen-Induced Signaling in Primary Rat Hippocampal Neurons(2008-07-01) Smith, Lonell T.; Simpkins, James; Das, Hriday K.; Machu, Tina K.Smith, Lonell T., Estrogen-Induced Signaling in Primary Rat Hippocampal Neurons. Masters (Biomedical Sciences). July 2008. 53 pages, 1 illustration, 7 figures. 37 titles. Abstract. The enhancing effects of 17-beta estradiol (E2) on performing cognitive tasks has been well demonstrated in laboratory mice, rats, and primates. Also there is ample clinical evidence indicating E2 enhances memory and reduces risk for Alzheimer’s disease. Furthermore, by increasing the capacity for long-term potentiation (LTP) in the hippocampus, E2 effectively increases the synaptic plasticity of this brain region in a manner that correlates with memory formation. The molecular mechanisms underlying LTP and synaptic plasticity have largely focused on the role of E2-induced signal transduction in the nucleus, and regulation of plasticity related gene expression at the transcriptional level. Conversely, the idea that E2-incuded signaling regulates at the level of translation and may play a role in these processes has yet to be explored. Recently, extracellular signal-regulated kinase (ERK) and mammalian target of rapamycin (mTOR) signaling pathways have been shown to couple synaptic activation to protein synthesis machinery. Here we investigate translational control by E2-induced ERK and mTOR signaling in primary neuronal culture. E2-induced signaling resulted in enhanced phosphorylation of ribosomal protein (S6) and eIF4E binding protein 1 (4EBP1) in an ERK and mTOR-dependent manner. Neuronal activity-dependent ERK and mTOR signaling have been shown to induce translation of a diverse array of dendritic resident mRNAs, including α-CaMKII and GluR1 subunits. Using a green fluorescent protein (GFP) translational reporter, we demonstrated that E2 stimulates GFP protein synthesis. We have also demonstrated that E2 treatment of hippocampal neurons increases surface expression of GluR1. Taken together, our results provide a mechanism by which E2 modulates the components necessary for persistent forms of LTP and long-term depression (LTD).