title: Localization of 14-3-3δ/ξ on the neuronal cell surface.
abstract: 14-3-3 proteins are intracellularly expressed as ubiquitous adaptor proteins. Here, we found localization of 14-3-3δ/ξ on the neuronal cell surface. 14-3-3δ/ξ was identified as a membrane target for 15-deoxy-Δ(12,14)-prostaglandin J2 (15d-PGJ2). 15d-PGJ2 is a pathological mediator of neurodegenerative diseases including Alzheimer's disease (AD). A causative peptide for AD, amyloid β, is one of binding partner of 14-3-3δ/ξ. Non-permeabilized neurons were used to avoid the intracellular effects of anti-14-3-3δ/ξ antibody in the present study. The plasmalemmal 14-3-3δ/ξ, but not the cytosolic one, was stimulated by its specific antibody, resulting in neuronal cell death. The neurotoxicity of anti-14-3-3δ/ξ antibody was suppressed by an antioxidant, catalase. Catalase prevented neurons from anti-14-3-3δ/ξ antibody-generating neurotoxic H2O2. The neuroprotective effect of catalase was also detected with the post-treatment of neurons after the application of anti-14-3-3δ/ξ antibody. Activation of mitogen-activated protein kinase signaling cascade is a down-stream consequence of H2O2 exposure. A c-Jun N-terminal kinase inhibitor suppressed anti-14-3-3δ/ξ antibody-induced neuronal cell death. To my knowledge, this is the first report that the antibody-stimulated plasmalemmal 14-3-3δ/ξ induced neuronal cell death. Furthermore, H2O2 and JNK contributed to the neurotoxicity of anti-14-3-3δ/ξ antibody as well as those of amyloid β and 15d-PGJ2.
authors.affiliation: Division of Physiology, Department of Pharmaceutical Health Care, Faculty of Pharmaceutical Sciences, Himeji Dokkyo University, 2-1, kami-ohno 7-Chome, Himeji, Hyogo 670-8524, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Yamamoto
authors.affiliation: Division of Physiology, Department of Pharmaceutical Health Care, Faculty of Pharmaceutical Sciences, Himeji Dokkyo University, 2-1, kami-ohno 7-Chome, Himeji, Hyogo 670-8524, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Koma
authors.affiliation: Division of Physiology, Department of Pharmaceutical Health Care, Faculty of Pharmaceutical Sciences, Himeji Dokkyo University, 2-1, kami-ohno 7-Chome, Himeji, Hyogo 670-8524, Japan. Electronic address: yagami@himeji-du.ac.jp.
authors.forename: Tatsurou
authors.initials: T
authors.lastname: Yagami
mesh_terms: D048948:14-3-3 Proteins / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D006861:Hydrogen Peroxide / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009474:Neurons; D018696:Neuroprotective Agents / Q000494:pharmacology; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D048948:14-3-3 Proteins; C097240:15-deoxy-delta(12,14)-prostaglandin J2; D016229:Amyloid beta-Peptides; D018696:Neuroprotective Agents; D006861:Hydrogen Peroxide; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D015230:Prostaglandin D2
keywords: 14-3-3δ/ξ; 15-Deoxy-Δ(12,14)-prostaglandin J(2); Alzheimer's disease; Catalase; Cortical neurons; Hydroxyl peroxide