DNA low-density array analysis of colchicine neurotoxicity in rat cerebellar granular neurons.
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 1 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.
Yeste-Velasco
Marc
M
Facultat de Farmàcia, Universitat de Barcelona, Nucli Universitari de Pedralbes, 08028 Barcelona, Spain.
Alvira
Daniel
D
Sureda
Francesc X
FX
Rimbau
Victor
V
Forsby
Anna
A
Pallàs
Mercè
M
Camins
Antoni
A
Folch
Jaume
J
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D002118:Calcium / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D002531:Cerebellum / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D003078:Colchicine / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D020869:Gene Expression Profiling / Q000379:methods*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015533:Transcriptional Activation / Q000187:drug effects*; D050257:Tubulin Modulators / Q000633:toxicity*
D050257:Tubulin Modulators; D003078:Colchicine; D002118:Calcium