Utilization of Pathway Modeling to Predict Changes in Sphingolipid Content During Granulocytic Differentiation of Retinoic Acid-induced HL60 cells

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Portz, Brent James
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Genomic analyses have the potential to provide insight to metabolic pathways and biomolecules that are important in cellular processes. This study used a recently developed tool (GenMAPP v2.1, www.genmapp.org adapted for the human sphingolipid biosynthesis pathway, www.sphingomap.org) to compare published gene expression data for HL60 cells, a human promyelocytic leukemia cell line, treated with retinoic acid to induce granulocytic differentiation. Based on the location and magnitude of changes in expression of genes for enzymes of sphingolipid metabolism in the context of this pathway model, granulocytic differentiation would be predicted to elevate de novo sphingolipid biosynthesis due to higher expression of serine palmitoyltransferase, with some interesting shifts in the way that the sphingoid base (sphinganine) is subsequently metabolized—such as that some may be incorporated into downstream metabolites such as ganglioside GD3. These predictions were tested and confirmed using thin layer chromatography. It is hoped this approach will help translate changes in gene expression for this pathway into a sphingolipidomic profile for the cells, and perhaps uncover interesting changes that can explain the behavior of these cells and possible therapeutic targets or biomarkers.
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Undergraduate Thesis
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