title: Evaluation of transcriptional activity of caspase-3 gene as a marker of acute neurotoxicity in rat cerebellar granular cells.
abstract: 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, 100microM and 1mM). 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.
authors.affiliation: Unitat de Bioquimica, Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili, C./St. Llorenç 21, 43201 Reus, Tarragona, Spain.
authors.forename: Jaume
authors.initials: J
authors.lastname: Folch
authors.forename: Daniel
authors.initials: D
authors.lastname: Alvira
authors.forename: Marta
authors.initials: M
authors.lastname: López-Querol
authors.forename: Marta
authors.initials: M
authors.lastname: Tajes
authors.forename: Francesc X
authors.initials: FX
authors.lastname: Sureda
authors.forename: Anna
authors.initials: A
authors.lastname: Forsby
authors.forename: Víctor
authors.initials: V
authors.lastname: Rimbau
authors.forename: Antoni
authors.initials: A
authors.lastname: Camins
authors.forename: Mercè
authors.initials: M
authors.lastname: Pallàs
mesh_terms: D000818:Animals; D015415:Biomarkers; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism*; D002531:Cerebellum / Q000166:cytology; D004305:Dose-Response Relationship, Drug; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism*; D009498:Neurotoxins / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014158:Transcription, Genetic / Q000187:drug effects*
chemical_list: D015415:Biomarkers; D009498:Neurotoxins; C505410:Casp3 protein, rat; D053148:Caspase 3