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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 …
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 …