DNA low-density array analysis of colchicine neurotoxicity in rat cerebellar granular neurons

Yeste-Velasco, Marc; Alvira, Daniel; Sureda, Francesc X.; Rimbau, Victor; Forsby, Anna; Pallas, Merce; Carnins, Antoni; Folch, Jaume


Cytoskeletal alteration is a key factor in neurodegenerative processes like Alzheimer's or Parkinson's disease. Colchicine is a microtubule-disrupting agent that binds to tubuline, inhibiting microtubule assembly, and which triggers apoptosis. The present research describes the transcriptional activation of molecules related to alternative forms of apoptosis, in an acute colchicine model of apoptosis in rat cerebellar granule neurons (CGNs). Treatment with colchicine up-regulated significantly the activity of genes related to oxidative stress: glutathione peroxidase I and catalase; altered significantly genes related to cell cycle control (cyclin D1 and cyclin-dependent kinase 2), genes related to classical apoptosis pathway (caspase 3) and a neuronal cell-related gene (pentraxin 1). Colchicine treatment also down-regulated the gene expression of calpain 1. In conclusion, our experiments demonstrate that the cell damage caused by exposure to colchicine activates the classical apoptosis pathway, but also promotes the up-regulation of several genes related to oxidative stress and cell cycle control. Present data may help to a better understanding of the molecular mechanisms involved in cytoskeletal degradation-induced apoptosis in neurons. (C) 2008 Elsevier Inc. All rights reserved.

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Título según WOS: ID WOS:000255614900012 Not found in local WOS DB
Título de la Revista: Neurotoxicology
Volumen: 29
Número: 2
Fecha de publicación: 2008
Página de inicio: 309
Página final: 317


Notas: ISI