title: Kainic Acid-Induced Golgi Complex Fragmentation/Dispersal Shifts the Proteolysis of Reelin in Primary Rat Neuronal Cells: An In Vitro Model of Early Stage Epilepsy.
abstract: The endoplasmic reticulum-lysosome-Golgi network plays an important role in Reelin glycosylation and its proteolytic processing. Golgi complex fragmentation is associated with the separation of Reelin from this network. Kainic acid (KA) is an excitotoxic agent commonly used to induce epilepsy in rodents. The relationship between KA-induced neuronal damage and Golgi complex fragmentation has not been investigated, leaving a major gap in our understanding of the molecular mechanism underlying the development of pathophysiology in epilepsy. We cultured primary rat cortical neurons eitherin ambient condition (control) or treated with a range of KA doses to reveal whether Golgi complex fragmentation impaired neuronal function. The half-life maximal inhibitory concentration (IC50) value of KA was detected to be approximately 5 μM, whereby at these concentrations, KA impaired neuronal viability, which was closely associated with initial Golgi complex fragmentation and subsequent reduction in both the expression and glycosylation patterns of Reelin. These findings implicate that Golgi complex fragmentation and Reelin dysfunction are key contributors to neuronal cell death in the early stage of epilepsy pathophysiology, thereby representing as novel disease biomarkers, as well as potent therapeutic targets for epilepsy.
authors: Center of Excellence for Aging and Brain, Department of Neurosurgery and Brain Repair, University of South Florida College of Medicine, 12901 Bruce B Downs Blvd, Tampa, FL, 33612, USA. ykaneko@health.usf.edu.
authors: Yuji
authors: Y
authors: Kaneko
authors: Center of Excellence for Aging and Brain, Department of Neurosurgery and Brain Repair, University of South Florida College of Medicine, 12901 Bruce B Downs Blvd, Tampa, FL, 33612, USA.
authors: Robert
authors: R
authors: Sullivan
authors: Center of Excellence for Aging and Brain, Department of Neurosurgery and Brain Repair, University of South Florida College of Medicine, 12901 Bruce B Downs Blvd, Tampa, FL, 33612, USA.
authors: Travis
authors: T
authors: Dailey
authors: Center of Excellence for Aging and Brain, Department of Neurosurgery and Brain Repair, University of South Florida College of Medicine, 12901 Bruce B Downs Blvd, Tampa, FL, 33612, USA.
authors: Fernando L
authors: FL
authors: Vale
authors: Center of Excellence for Aging and Brain, Department of Neurosurgery and Brain Repair, University of South Florida College of Medicine, 12901 Bruce B Downs Blvd, Tampa, FL, 33612, USA.
authors: Naoki
authors: N
authors: Tajiri
authors: Center of Excellence for Aging and Brain, Department of Neurosurgery and Brain Repair, University of South Florida College of Medicine, 12901 Bruce B Downs Blvd, Tampa, FL, 33612, USA. cborlong@health.usf.edu.
authors: Cesar V
authors: CV
authors: Borlongan
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000378:metabolism; D015153:Blotting, Western; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D004827:Epilepsy / Q000378:metabolism* / Q000473:pathology*; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D005632:Fructose / Q000031:analogs & derivatives / Q000494:pharmacology; D006056:Golgi Apparatus / Q000187:drug effects / Q000378:metabolism*; D007608:Kainic Acid / Q000494:pharmacology*; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D059748:Proteolysis / Q000187:drug effects*; D051381:Rats; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000378:metabolism*; D000077236:Topiramate
chemical_list: D001324:Autoantigens; D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; C097741:Golgin subfamily A member 2; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; C000717129:Reln protein, rat; D000077236:Topiramate; D005632:Fructose; D012697:Serine Endopeptidases; D007608:Kainic Acid
keywords: Glycosylation; Golgi protein; Initiating epilepsy; Kainic acid; Primary rat neuronal cell