title: APOEε4 increases trauma induced early apoptosis via reducing delayed rectifier K(+) currents in neuronal/glial co-cultures model.
abstract: Traumatic brain injury (TBI) is a commonly encountered emergency and severe neurosurgical injury. Previous studies have shown that the presence of the apolipoprotein E (APOE) ε4 allele has adverse outcomes across the spectrum of TBI severity. Our objective was to evaluate the effects of APOE alleles on trauma induced early apoptosis via modification of delayed rectifier K(+) current (Ik(DR)) in neuronal/glial co-cultures model. An ex vivo neuronal/glial co-cultures model carrying individual APOE alleles (ε2, ε3, ε4) of mechanical injury was developed. Flow cytometry and patch clamp recording were performed to analyze the correlations among APOE genotypes, early apoptosis and Ik(DR). We found that APOEε4 increased early apoptosis at 24h (p<0.05) compared to the ones transfected with APOEε3 and APOEε2. Noticeably, APOEε4 significantly reduced the amplitude of the Ik(DR) at 24h compared to the APOEε3 and APOEε2 (p<0.05) which exacerbate Ca(2+) influx. This indicates a possible effect of APOEε4 on early apoptosis via inhibiting Ik(DR) following injury which may adversely affect the outcome of TBI.
authors.affiliation: Department of Neurosurgery, the Affiliated Hospital of Luzhou Medical College, Luzhou 646000, PR China.
authors.forename: Ligang
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, PR China. Electronic address: sunxch1445@gmail.com.
authors.forename: Xiaochuan
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Neurosurgery, the Affiliated Hospital of Luzhou Medical College, Luzhou 646000, PR China; Department of Neurosurgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, PR China; Luzhou Medical College, Luzhou, 646000, PR China. Electronic address: jiangy0122@gmail.com.
authors.forename: Yong
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Neurosurgery, the Affiliated Hospital of Luzhou Medical College, Luzhou 646000, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Kuai
mesh_terms: D053327:Apolipoprotein E4 / Q000378:metabolism*; D017209:Apoptosis; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology*; D018920:Coculture Techniques; D051668:Delayed Rectifier Potassium Channels / Q000378:metabolism*; D004553:Electric Conductivity; D006801:Humans; D008954:Models, Biological; D009457:Neuroglia / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology
chemical_list: D053327:Apolipoprotein E4; D051668:Delayed Rectifier Potassium Channels
keywords: Apolipoprotein E; Delayed rectifier K(+) current; Early apoptosis; Genetics; Traumatic brain injury