QSB: Unraveling Palmitate-induced Apoptosis and Oleate-conferred Cytoprotection by Systems Analysis and RNA Interference

Michigan State University, East Lansing MI

Investigators

Abstract

0425821 Chan This research aims to test a hypothesis that plasma levels of fatty acids palmitate and oleate can have cytotoxic or cytoprotective effects in hepatocytes, respectively, and that by interfering with their respective biosynthetic pathways, one may modulate cell death or protection. In lipid metabolism, it has been shown that saturated fatty acids (e.g., palmitate) initiate apoptosis while unsaturated fatty acids (e.g., oleate) do not. In both cases, oxidation is the primary means of breakdown for these molecules. The presence of both saturated and unsaturated fatty acids appears to confer protection from apoptosis. The signaling cascades that result from metabolism of fatty acids have not, to date, been fully elucidated due to network complexity and interconnectivity that could not be deconvoluted by traditional biochemical methods. This research will leverage new high throughput capacity for information generation to help elucidate the mechanism by which the cellular fate is decided upon exposure to the palmitate and/or oleate, and thereby improve our understanding of how a cell chooses among the multiple possible pathways available to the cell. Two types of mathematical approaches will be used to analyze the data, feature extraction and Bayesian network analysis.