title: Mdivi-1 Protects Epileptic Hippocampal Neurons from Apoptosis via Inhibiting Oxidative Stress and Endoplasmic Reticulum Stress in Vitro.
abstract: Mitochondrial division inhibitor 1 (mdivi-1), a selective inhibitor of the mitochondrial fission protein dynamin-related protein 1, has been proposed to have a neuroprotective effect on hippocampal neurons in animal models of epilepsy. However, the effect of mdivi-1 on epileptic neuronal death in vitro remains unknown. Therefore, we investigated the effect of mdivi-1 and the underlying mechanisms in the hippocampal neuronal culture (HNC) model of acquired epilepsy (AE) in vitro. We found that mitochondrial fission was increased in the HNC model of AE and inhibition of mitochondrial fission by mdivi-1 significantly decreased neuronal apoptosis induced by AE. In addition, mdivi-1 pretreatment significantly attenuated oxidative stress induced by AE characterized by decrease of reactive oxygen species (ROS) production and malondialdehyde level and by increase of superoxide dismutase activity. Moreover, mdivi-1 pretreatment significantly decreased endoplasmic reticulum (ER) stress markers glucose-regulated protein 78, C/EBP homologous protein expression and caspase-3 activation. Altogether, our findings suggest that mdivi-1 protected against AE-induced hippocampal neuronal apoptosis in vitro via decreasing ROS-mediated oxidative stress and ER stress.
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, People's Republic of China.
authors.forename: Nanchang
authors.initials: N
authors.lastname: Xie
authors.affiliation: Department of Internal Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People's Republic of China.
authors.forename: Cui
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, People's Republic of China.
authors.forename: Chuanjie
authors.initials: C
authors.lastname: Wu
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, People's Republic of China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Cheng
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, People's Republic of China.
authors.forename: Yanlun
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, People's Republic of China.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, People's Republic of China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, People's Republic of China. hnxienanchang@163.com.
authors.forename: Yajun
authors.initials: Y
authors.lastname: Lian
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects / Q000502:physiology*; D004827:Epilepsy / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D052999:Quinazolinones / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C549041:3-(2,4-dichloro-5-methoxyphenyl)-2-sulfanyl-4(3H)-quinazolinone; D052999:Quinazolinones
keywords: Apoptosis; Epilepsy; Mdivi-1; Mitochondrial fission; Oxidative stress