title: Inhibition of Ectodermal-Neural Cortex 1 Protects Neural Cells from Apoptosis Induced by Hypoxia and Hypoglycemia.
abstract: Ectodermal-neural cortex 1 (Enc1), a member of the KELCH family, is widely expressed in the nervous system and plays an important role in nervous system development. However, the function of Enc1 in neural survival following apoptosis induced by hypoxia and hypoglycemia remains unclear. In this study, we aimed to investigate the role of Enc1 in the cell survival of neurons subjected to apoptosis induced by oxygen-glucose deprivation (OGD) and the potential underlying mechanism. The in vitro cell model of neuron OGD was established by anoxia/hypoglycemic injury. Real-time quantitative PCR and Western blot analyses showed that Enc1 was significantly reduced in neurons under anoxia/hypoglycemic injury. Knockdown of Enc1 by small interfering RNA markedly promoted the survival of neurons under anoxia/hypoglycemia. Moreover, knockdown of Enc1 inhibited neuronal apoptosis. Conversely, overexpression of Enc1 showed the opposite effect. Further, data demonstrated that Enc1 might regulate neuron survival through heme oxygenase-1 (HO-1) and nuclear factor erythroid 2-related factor (Nrf2). Taken together, our study suggests that knockdown of Enc1 protects newborn neurons from apoptosis induced by OGD associated with Nrf2 and HO-1, providing a novel molecular target for the treatment of neonatal apoptosis induced by hypoxia and hypoglycemia brain injury.
authors.affiliation: Department of Neonatal, The Third Affiliated Hospital, Xi'an Jiaotong University, Xi'an, 710068, China.
authors.forename: Hongtao
authors.initials: H
authors.lastname: Lei
authors.affiliation: Department of Traditional Chinese Medicine, Shaanxi Provincial People's Hospital, Xi'an, 710068, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Neonatal, The Third Affiliated Hospital, Xi'an Jiaotong University, Xi'an, 710068, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Department of Neonatal, The First Affiliated Hospital, Xi'an Jiaotong University, No. 277 West Yanta Street, Xi'an, 710061, China. sxliliu@163.com.
authors.forename: Li
authors.initials: L
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis; D015687:Cell Hypoxia; D002478:Cells, Cultured; D005947:Glucose / Q000172:deficiency* / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000378:metabolism; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D008840:Microfilament Proteins; D051267:NF-E2-Related Factor 2; D009479:Neuropeptides; C495637:Nfe2l2 protein, rat; D009687:Nuclear Proteins; C112302:ectodermal-neural cortex 1 protein; D006419:Heme Oxygenase (Decyclizing); D005947:Glucose; D010100:Oxygen
keywords: Enc1; HO-1; Neurons anoxia/hypoglycemic injury; Nrf2; siRNA