The transcription factor E2F1 modulates apoptosis of neurons

From National Research Council Canada

DOI	Resolve DOI: https://doi.org/10.1046/j.1471-4159.2000.0750091.x
Author	Search for: Hou, Sheng T.¹; Search for: Callaghan, Debbie; Search for: Fournier, Marie-Christine¹; Search for: Hill, Irene¹; Search for: Kang, Liping¹; Search for: Massie, Bernard²; Search for: Morley, Paul¹; Search for: Murray, Christine¹; Search for: Rasquinha, Ingrid¹; Search for: Slack, Ruth; Search for: MacManus, John P.¹
Affiliation	National Research Council of Canada. NRC Institute for Biological Sciences National Research Council of Canada. NRC Biotechnology Research Institute
Format	Text, Article
Subject	pharmaceutical; cortical neurons; apoptosis; E2F1; caspase; DNA fragmentation; replication-deficient adenovirus
Abstract	The transcription factor E2F1 is known to mediate apoptosis in isolated quiescent and postmitotic cardiac myocytes, and its absence decreases the size of brain infarction following cerebral ischemia. To demonstrate directly that E2F1 modulates neuronal apoptosis, we used cultured cortical neurons to show a temporal association of the transcription and expression of E2F1 in neurons with increased neuronal apoptosis. Cortical neurons lacking E2F1 expression (derived from E2F1 -/- mice) were resistant to staurosporine-induced apoptosis as evidenced by the significantly lower caspase 3-like activity and a lesser number of cells with apoptotic morphology in comparison with cortical cultures derived from wild-type mice. Furthermore, overexpressing E2F1 alone using replication-deficient recombinant adenovirus was sufficient to cause neuronal cell death by apoptosis, as evidenced by the appearance of hallmarks of apoptosis, such as the threefold increase in caspase 3-like activity and increased laddered DNA fragmentation, in situ endlabeled DNA fragmentation, and numbers of neuronal cells with punctate nuclei. Taken together, we conclude that E2F1 plays a key role in modulating neuronal apoptosis.
Publication date	2000-07
In	Journal of Neurochemistry 75, no. 1 (July 2000): 91–100.
Language	English
NRC number	42975 HOU2000
NPARC number	3538612
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Record identifier	8cac524e-b749-4f3c-97ad-86b090183c3f
Record created	2009-03-01
Record modified	2020-03-26

Date modified:: 2024-12-11