Evaluation of transcriptional activity of caspase-3 gene as a marker of acute neurotoxicity in rat cerebellar granular cells

Folch, Jaume; Alvira, Daniel; Lopez-Querol, Marta; Tajes, Marta; Sureda, Francesc X.; Forsby, Anna; Rimbau, Victor; Camins, Antoni; Pallas, Merce


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 16 h in complete medium containing the chemicals at three concentrations (10, 100 mu M 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. (C) 2009 Elsevier Ltd. All rights reserved.

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Título según WOS: ID WOS:000275991700017 Not found in local WOS DB
Título de la Revista: Toxicology in vitro : an international journal published in association with BIBRA.
Volumen: 24
Número: 2
Fecha de publicación: 2010
Página de inicio: 465
Página final: 471


Notas: ISI