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Medicine and Health Sciences

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University of Alabama at Birmingham

Theses/Dissertations

2006

Doctor of Philosophy (PhD) Heersink School of Medicine

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Increased Hexosamine Biosynthesis And Protein O-Glcnac Protect Isolated Rat Heart From Ischemia/Reperfusion Injury, Jia Liu Jan 2006

Increased Hexosamine Biosynthesis And Protein O-Glcnac Protect Isolated Rat Heart From Ischemia/Reperfusion Injury, Jia Liu

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Increased levels of protein-associated O-linked N-acetylglucosamine (O-GlcNAc) have been correlated with increased tolerance to stress. Therefore the goal of this study was to determine whether enhanced flux through the hexosamine biosynthesis pathway (HBP), which leads to elevated levels of O-GlcNAc, increased the tolerance of the heart to ischemia and reperfusion (I/R). Hearts from male rats were isolated and perfused with Krebs-Henseliet buffer containing 5mM glucose, and global, no-flow ischemia was induced for 20min followed by 60 min reperfusion. 20 min pre-treatment with 10 mM glucosamine, which enters the HBP directly, significantly improved functional recovery and decreased cardiac Troponin I release …


Modulation Of Cell Signaling By Tomoregulins In Embryogenesis And Cancer, Paul William Harms Jan 2006

Modulation Of Cell Signaling By Tomoregulins In Embryogenesis And Cancer, Paul William Harms

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Growth factor signals often regulate similar cellular processes both during embryogenesis and in adult homeostasis. Stringent control of these signals ensures proper embryonic development and correct cell physiology in mature individuals. Recently, a family of two members of Tomoregulin (or transmembrane protein with epidermal growth factor-like and two follistatin domains [TMEFF]) was found to interact with transforming growth factor-β (TGF-β) and ErbB signaling pathways, both of which are implicated in development and in cancer biology in the adult. The function as well as the mechanisms of TMEFFs in modulating these two signals has not been elucidated in detail. In this …


Klf4 Regulates Notch1 Expression And Signaling During Epithelial Transformation, Zhaoli Liu Jan 2006

Klf4 Regulates Notch1 Expression And Signaling During Epithelial Transformation, Zhaoli Liu

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Notch1 and KLF4 function in the specification of epithelial cell fates, and each can act as a context-dependent oncogene or tumor suppressor. We report that KLF4 directly regulates transcription of Notch1 and that cleavage of full-length Notch1 to the active intracellular form, N1IC, is necessary for transformation by KLF4. Paradoxically, KLF4 suppresses canonical Notch1-CSL signaling by up-regulating Hairless, an antagonist of this pathway. Dominant-negative inhibitors of the canonical Notch1 signaling pathway do not block transformation of epithelial cells by KLF4, while they greatly reduce the efficiency of transformation by N1IC. Thus, N1IC can transform cells by two distinct mechanisms: the …


Kiss1 Metastasis Suppressor Secretion Is Required For Metastasis Suppression, Kevin T. Nash Jan 2006

Kiss1 Metastasis Suppressor Secretion Is Required For Metastasis Suppression, Kevin T. Nash

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Failure to reduce the number of cancer deaths over the last 50 years is due to the inability to selectively target metastatic disease. Recently, the KISS1 metastasis suppressor has emerged as a promising molecular agent for the management of metastatic disease. Although KISS1 has been implicated in the regulation of the metastatic phenotype in human cancers and in in vivo mouse models, little is known about its mechanism. Recent evidence suggests that KISS1 is a neuropeptide that is processed and secreted to interact with its cognate receptor GPR54 in the hypothalamus to trigger puberty and maintain the reproductive state. However, …


Interference With Hiv-1 Primer Selection By Sirna Directed To The Hiv-1 Primer Binding Site, Wenlong Han Jan 2006

Interference With Hiv-1 Primer Selection By Sirna Directed To The Hiv-1 Primer Binding Site, Wenlong Han

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The replication of Human immunodeficiency virus type 1 (HIV-1) is characterized by the process of reverse transcription, which converts the viral RNA genome into a DNA intermediate prior to integration into the host cell chromosome. The initiation of reverse transcription needs a cellular tRNA primer, which binds to a region in the viral RNA genome, designated as the primer binding site (PBS). The 18-nucleotide PBS region of HIV-1, which is complementary to the 3′ terminal 18 nucleotides of tRNALys,3, is absolutely conserved among all HIV-1. The highly conserved PBS is a very good target for HIV-1 therapy. My dissertation research …


Regulation Of Ss-Catenin By Gli1 In Epithelial Transformation, Xingnan Li Jan 2006

Regulation Of Ss-Catenin By Gli1 In Epithelial Transformation, Xingnan Li

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Gli family members-mediated continuous Hedgehog (Hh) pathway activity plays a role in the growth of a number of human cancers, including the common malignancy of skin, basal cell carcinoma (BCC), and other highly aggressive tumor types. However, the mechanism by which Gli proteins act to promote the outgrowth of cancer in response to stimulation of Hh signaling is poorly understood. Identified as zinc finger transcriptional factors, the Gli family of proteins has been shown to be involved in multiple cellular processes through activating its target genes. Therefore, to study the function of Gli target genes is important for our understanding …