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A microarray study of MPP+-treated PC12 Cells: Mechanisms of toxicity (MOT) analysis using bioinformatics tools.

ABSTRACT: 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. CONCLUSION: 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.

SUBMITTER: Xu Z

PROVIDER: S-EPMC1637031 | biostudies-literature | 2005

REPOSITORIES: biostudies-literature

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A microarray study of MPP+-treated PC12 Cells: Mechanisms of toxicity (MOT) analysis using bioinformatics tools.

Xu Zengjun Z Patterson Tucker A TA Wren Jonathan D JD Han Tao T Shi Leming L Duhart Helen H Ali Syed F SF Slikker William W

BMC bioinformatics 20050715

<h4>Background</h4>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.<h4>Results</h4>In this study, Agilent rat oligo 22K microarrays were use ...[more]

PMID: 16026605

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Project description:Osteoarthritis (OA) is the most prevalent chronic degenerative disease that affects the health of the elderly. The present study aimed to identify significant genes involved in OA via bioinformatics analysis. A gene expression dataset (GSE104793) was downloaded from the Gene Expression Omnibus. Bioinformatics analysis was then performed in order to identify differentially expressed genes (DEGs) between untreated chondrocytes and chondrocytes cultured with interleukin-1β (IL-1β) for 24 h. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using Metascape. A protein-protein interaction network of DEGs was constructed using the Search Tool for the Retrieval of Interacting Genes. Gene set enrichment analysis (GSEA) was performed using GSEA software. Furthermore, chondrocytes were extracted and treated with IL-1β (10 ng/ml) for 24 h, and reverse-transcription quantitative PCR was used to confirm differential expression of hub genes. Patient samples were also collected to verify the bioinformatic analysis results. Based on the cut-off criteria used for determination of the DEGs, a total of 844 DEGs, including 498 upregulated and 346 downregulated DEGs, were identified. The DEGs were mainly enriched in the GO terms and KEGG pathways 'inflammatory response', 'negative regulation of cell proliferation', 'ossification', 'taxis', 'blood vessel morphogenesis', 'extracellular structure organization', 'mitotic cell cycle process' and 'TNF signaling pathway'. The majority of the PCR results, namely the differential expression of kininogen 2, complement C3, cyclin B1, cell division cycle 20, cyclin A2, 1-phosphatidylinositol 4-kinase, BUB1 mitotic checkpoint serine/threonine kinase, kinesin family member 11, cyclin B2 and BUB1 mitotic checkpoint serine/threonine kinase B were consistent with the bioinformatics results. Collectively, the present observations provided a regulation network of IL-1β-stimulated chondrocytes, which may provide potential targets of OA therapy.

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A microarray study of MPP+-treated PC12 Cells: Mechanisms of toxicity (MOT) analysis using bioinformatics tools.

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A microarray study of MPP+-treated PC12 Cells: Mechanisms of toxicity (MOT) analysis using bioinformatics tools.

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