title: Opposing roles for E2F1 in survival and death of cerebellar granule neurons.
abstract: The transcription factor E2F1 is upregulated when cerebellar granular neurons (CGNs) undergo apoptosis under potassium deprivation. In this study, we examined the effects of E2F1 upregulation on the survival and death of CGNs isolated from C57 mice and Sprague-Dawley (SD) rats. Plasmid- and adenovirus-mediated expression of E2F1 dose-dependently induced apoptosis in mouse CGNs but unexpectedly failed to induce apoptosis in rat CGNs. Caspase 3, a marker for neuronal apoptosis, was significantly activated by ectopic E2F1 expression in mouse CGNs but not in rat CGNs. Furthermore, overexpression of E2F1 significantly promoted apoptotic progression in mouse CGNs following potassium deprivation but attenuated apoptosis in rat CGNs, whereas E2F1 lacking DNA binding ability (E2F1-M132) lost its pro-apoptotic role in mouse CGNs and anti-apoptotic role in rat CGNs. Together, our results demonstrated that upregulation of E2F1 by potassium deprivation promotes apoptosis in C57 mouse CGNs but antagonizes apoptosis in SD rat CGNs, suggesting opposing roles for E2F1 in regulating CGN fate.
authors.affiliation: Department of Neurosurgery, Institute of Neuroscience, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, China. yzm@gzhmc.edu.cn
authors.forename: Zhongmin
authors.initials: Z
authors.lastname: Yuan
authors.forename: Lingling
authors.initials: L
authors.lastname: Yao
authors.forename: Mingchang
authors.initials: M
authors.lastname: Li
authors.forename: Shiming
authors.initials: S
authors.lastname: Liu
authors.forename: Weiwen
authors.initials: W
authors.lastname: He
authors.forename: Yongjian
authors.initials: Y
authors.lastname: Lu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D053148:Caspase 3 / Q000378:metabolism; D002461:Cell Line, Transformed; D002470:Cell Survival / Q000502:physiology*; D002531:Cerebellum / Q000378:metabolism / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D050687:E2F1 Transcription Factor / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D011188:Potassium / Q000009:adverse effects; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004268:DNA-Binding Proteins; D050687:E2F1 Transcription Factor; C493754:E2f1 protein, mouse; C493755:E2f1 protein, rat; D053148:Caspase 3; D011188:Potassium