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Articles 1 - 9 of 9
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Molecular Mechanisms Involved In Oligodendrocyte Development, Rochelle Coelho
Molecular Mechanisms Involved In Oligodendrocyte Development, Rochelle Coelho
Theses and Dissertations
Multiple sclerosis (MS) is a chronic disease of the central nervous system (CNS) characterized by demyelination and loss of oligodendrocytes (OLGs), the CNS myelin-producing cells. Thus, understanding the mechanisms that control OLG development can provide valuable knowledge regarding remyelination therapies for MS. This disease is thought to result from an autoimmune attack towards myelin. FTY720, an immunomodulator under evaluation for MS treatment is a sphingosine-1-phosphate (S1P) analog. We found before that S1P plays a crucial role in the NT-3-mediated survival of OLGs, an observation that led us to investigate whether FTY720 could have any effect on these cells. Our studies …
Regulation Of Mdm2 Mediated Nfκb2 Pathway In Human Lung Cancer, Lathika Mohanraj
Regulation Of Mdm2 Mediated Nfκb2 Pathway In Human Lung Cancer, Lathika Mohanraj
Theses and Dissertations
Overexpression of oncoprotein MDM2 and mutations of tumor suppressor p53 are frequently observed in human cancers. The NFκB pathway is one of the deregulated pathways in oncogenesis. The overall goal of the project was to study the regulation of NFκB pathway by MDM2 in lung cancer. Our first effort was to determine the frequency of MDM2 overexpression in human lung tumor samples and to identify co-occurring abnormal gene expression by studying the levels of MDM2 and members of NFκB pathway with respect to p53 status. Higher than normal levels of MDM2 were found in approximately 30% of the cancer samples …
Crosstalk Between Mdm2 And Akt Signaling Pathway In Oncogenesis., Mahesh Ramamoorthy
Crosstalk Between Mdm2 And Akt Signaling Pathway In Oncogenesis., Mahesh Ramamoorthy
Theses and Dissertations
MDM2, the human homologue of the Mouse Double Minute 2 gene product, has been shown to be over-expressed in many cancers and to induce tumorigenesis. The role of MDM2 in oncogenesis was thought to be p53 dependent. However recent years have shown MDM2 to be a key player in a complex network of interactions that affect cell cycle, apoptosis, and tumorigenesis in a p53 independent manner. Here we report a novel p53 independent role for the multidimensional protein MDM2; its ability to induce phosphorylation of Akt at serine 473 residue. Transient and stable over-expression of MDM2 in cultured cell lines …
Ceramide Kinase And Ceramide-1-Phosphate, Dayanjan Wijesinghe
Ceramide Kinase And Ceramide-1-Phosphate, Dayanjan Wijesinghe
Theses and Dissertations
Ceramide-1-phosphate (C1P) is a bioactive lipid that has been implicated in many biological processes. Our laboratory has conclusively demonstrated its role in inflammation via activation of cPLA2α. The only known enzyme to date responsible for direct synthesis of C1P is ceramide kinase. Very little was known about this enzyme in terms of its enzyme kinetics and substrate specificity. As CERK is an enzyme that acts on membrane lipids, its kinetics cannot be studied using standard bulk dilutions methods. Thus we developed a surface dilution approach using Triton X 100 mixed micelles for studying the kinetics of CERK. We discovered that …
The Response Of Hn4 Cells To Porphyromonas Gingivalis Dna, Cheyanne Warren
The Response Of Hn4 Cells To Porphyromonas Gingivalis Dna, Cheyanne Warren
Theses and Dissertations
Periodontal disease is one of the most common human diseases. Bacteria trigger the onset and progression of the disease and among them Porphyromonas gingivalis has been demonstrated to be a major etiologic agent. Although the interaction of the bacterium with the host is of major importance for the understanding of the disease mechanisms, both the host as well as the pathogen components involved in the interaction remain poorly understood. One of the bacterial components capable of eliciting a host response is unmethylated CpG DNA motifs found in bacteria. Thus, the first aim was to determine the response of oral epithelial …
Biological Functions Of The Novel Lysophosphatidic Acid (Lpa) Receptor, Lpa4/P2y9/Gpr23, Peilun Lee
Biological Functions Of The Novel Lysophosphatidic Acid (Lpa) Receptor, Lpa4/P2y9/Gpr23, Peilun Lee
Theses and Dissertations
Lysophosphatidic acid (LPA), a naturally occurring phospholipid present in serum and malignant effusions, elicits diverse biological functions through binding and activating specific cell surface G-protein coupled receptors. In addition to the conventional LPA1/Edg2, LPA2/Edg4 and LPA3/Edg7 receptors of the endothelial differentiation gene (Edg) family, LPA4/p2y9/GPR23 of the purinergic receptor family and the related LPA5/GPR92 and LPA6/p2y5 have been identified as novel LPA receptors. These newly identified LPA receptors are structurally distant from the Edg LPA1-3 receptors and couple to Gq, G12/13 and probably Gs subunits. However, the roles of the LPA4-6 receptors in LPA signal transduction and physiology are poorly …
Regulation Of Platelet-Activating Factor Acetylhydrolase By Oxidized Phospholipids And Proinflammatory Cytokines, Muralikrishna Mukkamala
Regulation Of Platelet-Activating Factor Acetylhydrolase By Oxidized Phospholipids And Proinflammatory Cytokines, Muralikrishna Mukkamala
Theses and Dissertations
Platelet-Activating Factor Acetylhydrolase (PAFAH) is a monocyte-derived phospholipase A2 that catalyzes the hydrolysis of platelet-activating factor (PAF) and has been implicated in atherosclerosis. Although PAF and other proinflammatory stimuli are postulated to induce the enzyme, mechanisms controlling PAFAH expression are largely unknown at present. We have shown that PAFAH induction in monocytes is increased in response to oxidized phospholipids. The PAFAH 5' flanking region has at least 10 putative Stat elements, and IL-6 has been shown to be downstream from the prostaglandin receptor, EP2, which has been shown to bind oxidized phospholipids, prompting the hypothesis that Stat proteins might regulate …
Fibronectin-Dependent Activation Of Camk-Ii Promotes Focal Adhesion Turnover By Inducing Tyrosine Dephosphorylation Of Fak And Paxillin, Charles Easley Iv
Fibronectin-Dependent Activation Of Camk-Ii Promotes Focal Adhesion Turnover By Inducing Tyrosine Dephosphorylation Of Fak And Paxillin, Charles Easley Iv
Theses and Dissertations
Transient elevations in Ca2+ have previously been shown to promote focal adhesion disassembly and cell motility. Yet the targets of these Ca2+ transients have not been fully examined. In this study, we demonstrate that CaMK-II, a Ca2+/calmodulin dependent protein kinase, is activated in response to β1 integrin engagement with fibronectin to influence fibroblast adhesion and motility. We also show that CaMK-II is dynamically localized to the cell surface using Total Internal Reflection Fluorescence microscopy (TIRFm) and that inhibition of CaMK-II with two mechanistically distinct, membrane permeant inhibitors accelerates spreading on fibronectin, enlarges paxillin-containing focal adhesions and …
Inflammation-Associated Gene Regulation In Primary Astrocytes, Glial Tumors And Cellular Differentiation, Katarzyna Marta Wilczynska
Inflammation-Associated Gene Regulation In Primary Astrocytes, Glial Tumors And Cellular Differentiation, Katarzyna Marta Wilczynska
Theses and Dissertations
This dissertation elucidates several independent molecular mechanisms that function in astrocytes and glial tumor cells, and suggest that developmental and inflammatory signals may contribute to the development of brain tumors. First, we analyzed the mechanism of TIMP-1 activation in astrocytes and glioblastoma cells. TIMP-1 expression is activated by IL-1, which is the major neuroinflammatory cytokine, via simultaneous activation of IKK/NF-kB and MEK3/6/p38/ATF-2 pathways in primary human astrocytes. In contrast to astrocytes, TIMP-1 is expressed at lower levels in glioblastomas, and is not regulated by IL-1 due to either dysfunctional IKK/NF-kB or MEK3/6/p38/ATF-2 activation. Thus, we propose a novel mechanism of …