A microarray study of MPP+-treated PC12 Cells: Mechanisms of toxicity (MOT) analysis using bioinformatics tools.
BACKGROUND
This paper describes a microarray study including data quality control, data analysis and the analysis of the mechanism of toxicity (MOT) induced by 1-methyl-4-phenylpyridinium (MPP+) in a rat adrenal pheochromocytoma cell line (PC12 cells) using bioinformatics tools. MPP+ depletes dopamine content and elicits cell death in PC12 cells. However, the mechanism of MPP+-induced neurotoxicity is still unclear.


RESULTS
In this study, Agilent rat oligo 22K microarrays were used to examine alterations in gene expression of PC12 cells after 500 muM MPP+ treatment. Relative gene expression of control and treated cells represented by spot intensities on the array chips was analyzed using bioinformatics tools. Raw data from each array were input into the NCTR ArrayTrack database, and normalized using a Lowess normalization method. Data quality was monitored in ArrayTrack. The means of the averaged log ratio of the paired samples were used to identify the fold changes of gene expression in PC12 cells after MPP+ treatment. Our data showed that 106 genes and ESTs (Expressed Sequence Tags) were changed 2-fold and above with MPP+ treatment; among these, 75 genes had gene symbols and 59 genes had known functions according to the Agilent gene Refguide and ArrayTrack-linked gene library. The mechanism of MPP+-induced toxicity in PC12 cells was analyzed based on their genes functions, biological process, pathways and previous published literatures.


CONCLUSIONS
Multiple pathways were suggested to be involved in the mechanism of MPP+-induced toxicity, including oxidative stress, DNA and protein damage, cell cycling arrest, and apoptosis.
Xu
Zengjun
Z
Division of Neurotoxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, 3900 NCTR Road, Jefferson, Arkansas 72079, USA. axu@genelogic.com
Patterson
Tucker A
TA
Wren
Jonathan D
JD
Han
Tao
T
Shi
Leming
L
Duhart
Helen
H
Ali
Syed F
SF
Slikker
William
W
D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity*; D000818:Animals; D019295:Computational Biology / Q000379:methods*; D016716:PC12 Cells; D040081:Protein Array Analysis / Q000379:methods*; D051381:Rats
D015655:1-Methyl-4-phenylpyridinium