Paraquat-induced apoptotic cell death in cerebellar granule cells.
We examined the toxicity of paraquat, a possible environmental risk factor for neurodegenerative disorders like Parkinson's disease (PD). Paraquat is structurally similar to the neurotoxin MPP+ that can induce Parkinsonian-like features in rodents, non-human primates and human. Exposure of cerebellar granule cells to relatively low concentrations of paraquat (5 microM) produces apoptotic cell death with a reduction in mitochondrial cytochrome c content, proteolytic activation and caspase-3 activity increase and DNA fragmentation. Paraquat-induced apoptosis was significantly attenuated by co-treatment of cerebellar granule cells with the radical scavenger vitamin E, suggesting that paraquat-induced free radicals serve as important signal in initiation of cell death. As a decrease in mitochondrial cytochrome c content is also prevented by allopurinol, we suggest that xanthine oxidase plays an important role in the free radical production that precedes the apoptotic cascade and cell death after paraquat exposition.
González-Polo
Rosa A
RA
Departamento de Bioquímica y Biología Molecular y Genética, Facultad de Veterinaria, Universidad de Extremadura, Cáceres, Spain.
Rodríguez-Martín
Andrea
A
Morán
José M
JM
Niso
Mireia
M
Soler
Germán
G
Fuentes
José M
JM
D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western / Q000379:methods; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology* / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006540:Herbicides / Q000633:toxicity; D020287:In Situ Nick-End Labeling / Q000379:methods; D008297:Male; D008928:Mitochondria / Q000187:drug effects; D008954:Models, Biological; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D010269:Paraquat / Q000633:toxicity*; D010879:Piperazines / Q000737:chemistry / Q000633:toxicity; D051381:Rats; D013778:Tetrazolium Salts; D013844:Thiazoles; D013997:Time Factors; D014810:Vitamin E / Q000494:pharmacology
D004791:Enzyme Inhibitors; D006540:Herbicides; D010879:Piperazines; D013778:Tetrazolium Salts; D013844:Thiazoles; C096490:1,1-dimethyl-4-(2-quinolyl)piperazinium; D014810:Vitamin E; D000493:Allopurinol; D045304:Cytochromes c; C505407:CASP3 protein, human; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; C022616:thiazolyl blue; D010269:Paraquat