Digital Commons Network^™

The Role Of Secreted Phosphoprotein-24 In Osteoblast Differentiation And Matrix Mineralization, Samuel Ramage

Theses and Dissertations

Secreted Phosphoprotein-24 (Spp24) was initially isolated and characterized as a component of bovine cortical bone matrix. Subsequent characterization has shown it is multiply phosphorylated and homologous to cystatin and TGF-β receptor type II. Spp24 is a minor component of the serum fetuin mineral complex that binds calcium-phosphate minerals and prevents their deposition. The TGF-β receptor homology domain binds BMP-2 weakly in vitro and enhances BMP-2’s osteogenic effects in vivo. The ability of Spp24 to affect BMP activity suggests an important role for Spp24 as a native, bioactive componentof bone that regulates bone development.

Spp24 was highly up-regulated in rat cortical …

The Ksga Methyltransferase: Characterization Of A Universally Conserved Protein Involved In Robosome Biogenesis, Heather Colleen O'Farrell

Theses and Dissertations

The KsgA enzymes comprise an ancient family of methyltransferases that are intimately involved in ribosome biogenesis. Ribosome biogenesis is a complicated process, involving numerous cleavage, base modification and assembly steps. All ribosomes share the same general architecture, with small and large subunits made up of roughly similar rRNA species and a variety of ribosomal proteins. However, the fundamental assembly process differs significantly between eukaryotes and eubacteria, not only in distribution and mechanism of modifications but also in organization of assembly steps. Despite these differences, members of the KsgA/Dim1 methyltransferase family and their resultant modification of small-subunit rRNA are found throughout …

The Influence Of Adenoviral Infection And The Group Via Calcium-Independent Phospholipase A2 On Hepatic Lipid Metabolism, William Palmer Wilkins Iii

Theses and Dissertations

Sterol regulatory element-binding proteins (SREBP) are transcription factors that regulate genes involved in lipid metabolism especially in the liver. Therefore, hepatic SREBP is significant regulator of systemic lipid metabolism. Evidence demonstrates that insulin and dietary unsaturated fatty acid (UFA) regulate SREBP1 expression and subsequent SREBP1-mediated gene transcription, events that in many instances result in modulation of systemic fatty acid and triglyceride (TG) homeostasis. A series of investigations was designed to uncover novel regulators of SREBP1. Dietary and exogenous addition of UFA has been shown to regulate SREBP function yet, an endogenous source of UFA capable of modulating SREBP remains elusive. …

The Role Of Sphingosine Kinase 2 In Cell Growth And Apoptosis, Heidi M. Sankala

Theses and Dissertations

Two isoforms of sphingosine kinase (SphK) catalyze the formation of sphingosine-1-phosphate (SIP). Whereas, SphKl stimulates cell growth and survival, it was found that when overexpressed in mouse NIH 3T3 fibroblasts SphK2 enhances caspase-dependent apoptosis in response to serum deprivation, independently of S1P receptors. Sequence analysis revealed that SphK2 contains a 9 amino acid motif similar to that present in BH3-only proteins. Studies showed that the BH3-only domain, catalytic activity, endoplasmic reticulum (ER) stress, and uptake of calcium by the mitochondria may all contribute to the apoptotic effects of overexpressed SphK2 in NIH 3T3 cells. Further studies in human carcinoma cells …

Role Of Ceramide-1-Phosphate As A Specific And Potent Activator Of Group Iva Cytosolic Phospholipase A2 Alpha, Preeti Subramanian

Theses and Dissertations

Eicosanoids are potent mediators of inflammatory response whose role has been well established in inflammatory disorders. Release of arachidonic acid by group IVA cytosolic phospholipase A2 α (cPLA2α) is the initial rate limiting step for the production of eicosonoids in response to inflammatory mediators. Previous findings from our laboratory have demonstrated that cPLA2α is directly activated by the emerging bioactive sphingolipid, ceramide-1-phosphate (C1P). In this study, we have developed a modified Triton X-100/phosphatidylcholine (PC) mixed micelle assay which was utilized to determine the kinetics and specificity of this lipid-enzyme interaction. Using this assay, the activity of the enzyme increased in …