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 μM 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

Communities and change in the anthropocene: understanding social-ecological vulnerability and planning adaptations to multiple interacting exposures

The majority of vulnerability and adaptation scholarship, policies and programs focus exclusively on climate change or global environmental change. Yet, individuals, communities and sectors experience a broad array of multi-scalar and multi-temporal, social, political, economic and environmental changes to which they are vulnerable and must adapt. While extensive theoretical-and increasingly empirical-work suggests the need to explore multiple exposures, a clear conceptual framework which would facilitate analysis of vulnerability and adaptation to multiple interacting socioeconomic and biophysical changes is lacking. This review and synthesis paper aims to fill this gap through presenting a conceptual framework for integrating multiple exposures into vulnerability analysis and adaptation planning. To support applications of the framework and facilitate assessments and comparative analyses of community vulnerability, we develop a comprehensive typology of drivers and exposures experienced by coastal communities. Our results reveal essential elements of a pragmatic approach for local-scale vulnerability analysis and for planning appropriate adaptations within the context of multiple interacting exposures. We also identify methodologies for characterizing exposures and impacts, exploring interactions and identifying and prioritizing responses. This review focuses on coastal communities; however, we believe the framework, typology and approach will be useful for understanding vulnerability and planning adaptation to multiple exposures in various social-ecological contexts