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Evaluation of transcriptional activity of caspase-3 gene as a marker of acute neurotoxicity in rat cerebellar granular cells
Unitat de Bioquimica, Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili, Tarragona, Spain.
Unitat de Farmacologia i Farmacognòsia and Institut de Biomedicina (IBUB), Facultat de Farmàcia, Universitat de Barcelona, Nucli Universitari de Pedralbes, Barcelona, Spain.
Unitat de Farmacologia, Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili, Tarragona, Spain.
Unitat de Farmacologia i Farmacognòsia and Institut de Biomedicina (IBUB), Facultat de Farmàcia, Universitat de Barcelona, Nucli Universitari de Pedralbes, Barcelona, Spain.
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2010 (English)In: Toxicology in Vitro, ISSN 0887-2333, E-ISSN 1879-3177, Vol. 24, no 2, 465-471 p.Article in journal (Refereed) Published
Abstract [en]

Caspase-3 is a key protein involved in the classical apoptosis mechanism in neurons, as in many other cells types. In the present research, we describe the transcriptional activity of caspase-3 gene as a marker of acute toxicity in a primary culture model of rat cerebellar granule neurons (CGNs). CGNs were incubated for 16h in complete medium containing the chemicals at three concentrations (10, 100 μM and 1 mM). A total of 48 different compounds were tested. Gene transcriptional activity was determined by low-density array assays, and by single Taqman caspase-3 assays. Results from the PCR arrays showed that the caspase-3 gene was up-regulated when CGNs were exposed to neurotoxic chemicals. Significative correlations were found between the transcriptional activity of caspase-3 and the activity of some other genes related to apoptosis, cell-cycle and ROS detoxification. In our experiments, acute exposure of CGNs to well-documented pro-apoptotic xenobiotics modulated significantly caspase-3 gene expression, whereas chemicals not related to apoptosis did not modify caspase-3 gene expression. In conclusion, acute exposure of CGNs to neurotoxic compounds modulates the transcriptional activity of genes involved in the classical apoptotic pathway, oxidative stress and cell-cycle control. Transcriptional activity of caspase-3 correlates significantly with these changes and it could be a good indicator of acute neurotoxicity.

Place, publisher, year, edition, pages
2010. Vol. 24, no 2, 465-471 p.
Keyword [en]
Apoptosis, Cell-cycle, Caspase-3, Oxidative stress, Cerebellar granule neurons, Acute toxicity
National Category
Natural Sciences
Research subject
Neurochemistry and Neurotoxicology; Neurochemistry and Molecular Neurobiology
Identifiers
URN: urn:nbn:se:su:diva-32263DOI: 10.1016/j.tiv.2009.09.023ISI: 000275991700017PubMedID: 19815060OAI: oai:DiVA.org:su-32263DiVA: diva2:279977
Note
authorCount :9Available from: 2009-12-07 Created: 2009-12-07 Last updated: 2017-12-12Bibliographically approved

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