Chip
Exploring Neurotoxicity with Gene Expression Microarrays
A review of A microarray study of MPP+-treated PC12 Cells: Mechanisms of toxicity (MOT) analysis using bioinformatics tools.
Note: This is a review of the published article listed below. All information, quotes, figures, methods, and findings mentioned in this review are from that article, and are the property of its authors and/or the publication in which the article originally appeared.
A joint effort between the Toxicological Research division of FDA and the Advanced Center for Genome Toxicology by Xu, et al (2005) describes the mechanism of toxicity (MOT) induced by 1-methyl-4-phenylpyridinium (MPP+), a MPTP (1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine) precursor, in the PC12 rat cell line that serves as Parkinson’s Disease (PD) model. The group used the Agilent rat 60-mer oligonucleotide 22K microarray to examine gene expression alterations and better understand mechanisms of MPP+-induced toxicity. Multiple pathways appear to be involved — oxidative stress, DNA and protein damage, cell growth arrest, and apoptosis. IRIDESCENT analysis was used to demonstrate a correlation to genes involved in MPTP-induced neurotoxicity in both mice and PD. In addition, shared relationship analysis identified the compound methyl methanesulfonate (MMS) as being highly related to the responding genes, opening avenues of future exploration.
Figure 1. Genes altered by MPP+ treatment
Red- and green-labeled spots represent genes with log values ≥ 1 (2-fold and above increase) and ≤ N1 (2-fold and above decrease), respectively. The average correlation of treated/control log (base 2) of two sample pairs after dye-swapped slides indicates low variance between sample sets. A two-fold cutoff was applied as significant. In total, there were 106 genes (44 induced and 62 repressed) that exhibited = two-fold change in expression upon MPP+ treatment. Low sample set variance between samples allows usage of fold-change criteria to determine gene alteration.
Figure 2. Complex gene response network in MPP+-treated cells.
Within the gene subset expressed at = two-fold in MPTP microarray experiments, 13 genes were found colinked within MEDLINE abstracts > twice (Green ovals represent down-regulated genes, red ovals represent upregulated genes). Relationships betweem MPTP (octagon) and Parkinson's Disease (rectangle) are also displayed. This literature analysis called the most attention to the DNA damage pathway, with GADD45 and GADD153 in relatively central roles.
Title: A microarray study of MPP+-treated PC12 Cells: Mechanisms of toxicity (MOT) analysis using bioinformatics tools.
Authors: Xu Z, Patterson TA, Wren JD, Han T, Shi L, Duhart H, Ali SF, Slikker W Jr
Journal: BMC Bioinformatics. 2005 Jul 15;6 Suppl 2:S8.
More