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Series GSE5023

Query DataSets for GSE5023

Status

Public on Jul 27, 2006

Title

The Insecticides Cyfluthrin & Chlorpyrifos Alter Expression of Genes with Diverse Functions in Primary Human Astrocytes

Organism

Homo sapiens

Experiment type

Expression profiling by array

Summary

Given the widespread use of insecticides in the environment, it is important to perform studies evaluating their potential effects on humans. Organophosphate insecticides, such as chlorpyrifos, are being phased out; however, the use of pyrethroids in household pest control is increasing. While chlorpyrifos is relatively well studied, much less is known about the potential neurotoxicity of cyfluthrin and other pyrethroids. To gain insights into the neurotoxicity of cyfluthrin, we compared and evaluated the toxicity profiles of chlorpyrifos and cyfluthrin in primary human fetal astrocytes. We found that at the same concentrations, cyfluthrin exerts as great as, or greater toxic effects on the growth, survival, and proper functioning of human astrocytes. By using microarray gene expression profiling, we systematically identified and compared the potential molecular targets of chlorpyrifos and cyfluthrin, at a genome-wide scale. We found that chlorpyrifos and cyfluthrin targeted a similar number of transcripts. These targets include chaperones, signal transducers, transcriptional regulators, transporters, and those involved in behavior and development. Further computational and biochemical analyses suggest that cyfluthrin and chlorpyrifos up-regulated certain targets of the interferon-gamma and insulin signaling pathways, and that they increased the protein levels of activated ERK1/2, a key component of insulin signaling; IL-6, a key inflammatory mediator; and GFAP, a marker of inflammatory astrocyte activation. These results suggest that inflammatory activation of astrocytes might be an important mechanism underlying neurotoxicity of both chlorpyrifos and cyfluthrin.
Keywords: treatment comparison

Overall design

Primary human fetal astrocytes treated with 25 uM cyfluthrin, 25 uM chlorpyrifos, or no insecticide for 7 days were collected. Total RNA was extracted by using TRIzol reagent (GIBCOBRL Life Technologies). The synthesis of cDNAs and biotin-labeled cRNAs were carried out exactly as described in the Affymetrix GeneChip Expression Analysis Technical Manual (2000). The human genome U133 plus 2.0 arrays were purchased from Affymetrix, Inc. Probe hybridization and data collection was carried out by the Columbia University Affymetrix GeneChip processing center. Specifically, the Affymetrix GeneChip Hybridization Oven 640 and the next generation GeneChip Fluidics Station 450 were used for hybridization and chip processing. Chip scanning was performed by using the GeneChip scanner 3000. Initial data analysis was performed by using the Affymetrix GCOS1.2 software.

Contributor(s)

Zhang L, Mense S

Citation(s)

16790487

Submission date

Jun 08, 2006

Last update date

Mar 25, 2019

Contact name

Sarah Mense

E-mail(s)

smm2123@columbia.edu