Item – Theses Canada

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Wishart, Alexander D.(Alexander David),1982-
Quercetin-3-glucoside mediates cytoprotection in SH-SY5Y cells against H₂O₂ induced oxidative stress by inducing cholesterol biosynthesis.
M. Sc. -- Dalhousie University, 2006
Ottawa : Library and Archives Canada = Bibliothèque et Archives Canada, [2007]
2 microfiches
Includes bibliographical references.
Quercetin-3-glucoside (Q3G) is a natural product with strong antioxidant activity. In human neuroblastoma SH-SY5Y cells, H2O2 mediated oxidative stress leads to decreased cell viability, increased intracellular reactive oxygen species and cell death. Pretreatment with Q3G reverses these effects of oxidative stress. Although Q3G and related compounds are well documented cytoprotectants, the mechanism responsible for this beneficial effect is unclear. Gene expression profiling using cDNA microarrays was performed to document transcriptional changes resulting from exposure to either just Q3G or the effects of pretreatment with Q3G on the genomic response to oxidative stress. Only in cells pretreated with Q3G and then exposed to oxidative stress was there a large increase in the number of genes associated with cholesterol biosynthesis as well as an elevation of cholesterol levels. Mevastatin, an inhibitor of cholesterol biosynthesis, reversed both the elevation of cholesterol and cytoprotection produced by oxidative stress in cells pretreated with Q3G. These findings suggest that pre-incubation with Q3G increased resistance to the injurious effects of H2O2 by enabling SH-SY5Y cells to mount a protective response to oxidative stress by elevating cholesterol synthesis.