Effects of the protein kinase inhibitor PKC412 on gene expression and link to physiological effects in zebrafish Danio rerio eleuthero-embryos

Oggier, D. M. and Lenard, A. and Kury, M. and Hoger, B. and Affolter, M. and Fent, K.. (2010) Effects of the protein kinase inhibitor PKC412 on gene expression and link to physiological effects in zebrafish Danio rerio eleuthero-embryos. Toxicological sciences, Vol. 119, H. 1. pp. 104-115.

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Official URL: http://edoc.unibas.ch/dok/A5842466

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To identify molecular effects of the antineoplastic agent PKC412 (Midostaurin), we applied gene expression profiling in zebrafish using whole genome microarrays. Behavioral, developmental and physiological effects were investigated in order to analyze for correlations between altered gene-expression profiles with effects on development and physiology. Zebrafish blastula-stage embryos were exposed for 6 days post fertilization (dpf) to nominal levels of 2 mug/L and 40 mug/L PKC412. Among the 259 and 511 altered transcripts at both concentrations, respectively, the expressions of genes involved in the circadian rhythm were further investigated. Alteration of swimming behavior was not observed. Pathways of interest affected by PKC412 were angiogenesis, apoptosis, DNA damage response and response to oxidative stress. Angiogenesis was analyzed in double transgenic zebrafish embryos Tg(fli1a:EGFP)y1;Tg(gata1:dsRed)sd2; no major defects were induced by PKC412 treatment at both concentrations. Apoptosis occurred in olfactory placodes of embryos exposed to 40 mug/L, and DNA damage was induced at both PKC412 concentrations. However, there were no significant effects on reactive oxygen species formation. This study leads to the conclusion that PKC412-induced alterations of gene transcripts are partly paralleled by physiological effects at high, but not at low PKC412 concentrations expected to be of environmental relevance.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Growth & Development > Cell Biology (Affolter)
UniBasel Contributors:Affolter, Markus
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Oxford University Press
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:08 Jun 2012 06:56
Deposited On:08 Jun 2012 06:49

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