Increased expression of the transcription factor E2F1 during dopamine-evoked, caspase-3-mediated apoptosis in rat cortical neurons.
The transcription factor E2F1 mRNA and protein levels increased in rat cortical neurons in response to dopamine (DA)- or 6-hydroxydopamine (OHDA)-evoked apoptosis. Increased E2F1 protein was detected in the nucleus of neurons by double fluorescent immunocytochemistry using antibodies to E2F1 and NeuN. DA and 6-OHDA induced caspase-3-mediated apoptosis of cortical neurons which was attenuated by the addition of antioxidants or caspase-3 inhibitors to the cultures. Antioxidants prevented DA-evoked neuronal apoptosis, and also attenuated the increase in E2F1 expression. These findings suggest that increased expression of the transcription factor E2F1 may serve as a death signal during DA-evoked neuronal apoptosis.
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Institute for Biological Sciences, National Research Council Canada, Building M-54, 1500 Montreal Road, Ottawa, Ontario, K1A 0R6, Canada. sheng.hou@nrc.ca
Cowan
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Dostanic
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Rasquinha
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Comas
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Morley
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MacManus
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JP
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002352:Carrier Proteins; D053148:Caspase 3; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism*; D018797:Cell Cycle Proteins; D002540:Cerebral Cortex / Q000166:cytology; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004268:DNA-Binding Proteins; D004298:Dopamine / Q000494:pharmacology*; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D015870:Gene Expression / Q000502:physiology; D009474:Neurons / Q000166:cytology* / Q000201:enzymology; D009842:Oligopeptides / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D056465:Retinoblastoma-Binding Protein 1; D014157:Transcription Factors / Q000235:genetics*
D000975:Antioxidants; D002352:Carrier Proteins; D061945:Caspase Inhibitors; D018797:Cell Cycle Proteins; D015853:Cysteine Proteinase Inhibitors; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493755:E2f1 protein, rat; D009842:Oligopeptides; D012333:RNA, Messenger; D056465:Retinoblastoma-Binding Protein 1; D014157:Transcription Factors; C110772:benzoylcarbonyl-aspartyl-glutamyl-valyl-aspartyl-fluoromethyl ketone; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D004298:Dopamine