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Title: Global Gene expression changes caused by neurotoxins
Keywords: Candoxin, Sarin or GB, Microarray, Neurodegeneration, Global gene-expression and Neurotoxins.
Issue Date: 19-Jan-2007
Citation: PACHIAPPAN ARJUNAN (2007-01-19). Global Gene expression changes caused by neurotoxins. ScholarBank@NUS Repository.
Abstract: This study aims to explore the mechanism/s of neurodegeneration after exposure to neurotoxins, candoxin (CDX; PDB #1JGK) and sarin (GB). Gene expression profiles of human Hs683 and SH-SY5Y neuronal cells exposed to CDX and GB, respectively were studied using Affymetrix GeneChips. Genes altered by a?Y3-fold (105 for CDX and 370 for GB treatments) were selected by GeneSpring analyses. CDX altered genes involved in signal transduction, ubiquitin-inflammation, mitochondrial-dysfunction, and damage-response pathways. Using qRT-PCR and specific CDX-binding peptide, IL7R, IL13RA2, IL-1i??, TNFRSF12A, GADD45A, CD44 and IFI44 were identified as genes that might play an important role in CDX-induced glial-inflammation. A single GB dose caused a reversible down-regulation of genes related to neurodegeneration. The effect was irreversible with repeated GB doses. qRT-PCR and immunoblotting confirmed the reduced expression of presenilin-1 & 2, I?2M, CD9, Ets-2, APOE and DDC mRNA and proteins. This study showed the possible mechanism/s of neurodegeneration after exposure to neurotoxins.
Appears in Collections:Ph.D Theses (Open)

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