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ALTERED TRANSCRIPTIONAL RESPONSES OF MOUSE EMBRYO CULTURES EXPOSED TO BISINDOLYLMALEIMIDE (BIS L)
Citation:
Karoly, E. D., J E. Schmid, M R. Blanton, AND E S. Hunter III. ALTERED TRANSCRIPTIONAL RESPONSES OF MOUSE EMBRYO CULTURES EXPOSED TO BISINDOLYLMALEIMIDE (BIS L). Presented at Society of Toxicology, New Orleans, LA, March 6-10, 2005.
Description:
Altered transcriptional responses in mouse embryos exposed to bisindolylmaleimide I (Bis I) in whole embryo culture
Edward D. Karoly?*, Judith E. Schmid*, Maria R. Blanton*and E. Sidney Hunter III*
?Curriculum in Toxicology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina and *Reproductive Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. EPA, RTP, North Carolina 27711
Protein kinase C (PKC) comprises a large family of serine/threonine kinases which are involved in a multitude of physiological processes regulating cell proliferation and differentiation. Bisindolylmaleimide I (Bis I), a specific PKC inhibitor, was utilized in this study to examine the transcriptional responses to PKC inhibition in mouse embryos during neurulation. CD-1 mouse embryos (3 to 6 somite stage) were exposed to 10?M Bis I for 0, 1, 3 or 6h using whole embryo culture. At these times 10-15 embryonic heads were removed and pooled for total RNA isolation. Biotinylated cRNA was prepared using GeneChip one-cycle target labeling and hybridized to GeneChip Mouse Genome 430 2.0 arrays (Affymetrix, Inc., Santa Clara, CA). Two-way ANOVA identified 3,207 genes (of 34,000 transcripts on the array) as being differentially expressed across dose and/or time. Pathway analysis of these genes identified numerous pathways as affected by the treatment with Bis I including apoptosis, Wnt signaling and oxidative phosphorylation. Gene Ontology (GO) analysis of molecular function identified an extensive list of genes associated with binding events and catalytic activity. Cluster analysis and linear models were used to further identify the transcriptional responses in mouse embryos exposed to Bis I and their association with embryotoxicity. This is an abstract of a proposed presentation and does not necessarily reflect EPA policy. Funded by EPA/UNC Toxicology research program, training agreement CT 827206 with the Curriculum of Toxicology, University of North Carolina at Chapel Hill, North Carolina.