title: Histone deacetylase inhibitor attenuates neurotoxicity of clioquinol in PC12 cells.
abstract: Clioquinol is considered to be a causative agent of subacute myelo-optico neuropathy (SMON), although the pathogenesis of SMON is yet to be elucidated. We have previously shown that clioquinol inhibits nerve growth factor (NGF)-induced Trk autophosphorylation in PC12 cells transformed with human Trk cDNA. To explore the further mechanism of neuronal damage by clioquinol, we evaluated the acetylation status of histones in PC12 cells. Clioquinol reduced the level of histone acetylation, and the histone deacetylase (HDAC) inhibitor Trichostatin A upregulated acetylated histones and prevented the neuronal cell damage caused by clioquinol. In addition, treatment with HDAC inhibitor decreased neurite retraction and restored the inhibition of NGF-induced Trk autophosphorylation by clioquinol. Thus, clioquinol induced neuronal cell death via deacetylation of histones, and HDAC inhibitor alleviates the neurotoxicity of clioquinol. Clioquinol is now used as a potential medicine for malignancies and neurodegenerative diseases. Therefore, HDAC inhibitors can be used as a candidate medicine for the prevention of its side effects on neuronal cells.
authors.affiliation: Department of Neurology, Fujita Health University School of Medicine, 1-98 Kutsukake-cho, Toyoake, Aichi 470-1192, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Fukui
authors.affiliation: Department of Neurology, Fujita Health University School of Medicine, 1-98 Kutsukake-cho, Toyoake, Aichi 470-1192, Japan. Electronic address: kasakura@fujita-hu.ac.jp.
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Asakura
authors.affiliation: Department of Neurology, Fujita Health University School of Medicine, 1-98 Kutsukake-cho, Toyoake, Aichi 470-1192, Japan.
authors.forename: Chika
authors.initials: C
authors.lastname: Hikichi
authors.affiliation: Department of Neurology, Fujita Health University School of Medicine, 1-98 Kutsukake-cho, Toyoake, Aichi 470-1192, Japan.
authors.forename: Tomomasa
authors.initials: T
authors.lastname: Ishikawa
authors.affiliation: Department of Neurology, Fujita Health University School of Medicine, 1-98 Kutsukake-cho, Toyoake, Aichi 470-1192, Japan.
authors.forename: Rie
authors.initials: R
authors.lastname: Murai
authors.affiliation: Department of Neurology, Fujita Health University School of Medicine, 1-98 Kutsukake-cho, Toyoake, Aichi 470-1192, Japan.
authors.forename: Seiko
authors.initials: S
authors.lastname: Hirota
authors.affiliation: Department of Neurology, Fujita Health University School of Medicine, 1-98 Kutsukake-cho, Toyoake, Aichi 470-1192, Japan.
authors.forename: Ken-Ichiro
authors.initials: K
authors.lastname: Murate
authors.affiliation: Department of Neurology, Fujita Health University School of Medicine, 1-98 Kutsukake-cho, Toyoake, Aichi 470-1192, Japan.
authors.forename: Madoko
authors.initials: M
authors.lastname: Kizawa
authors.affiliation: Department of Neurology, Fujita Health University School of Medicine, 1-98 Kutsukake-cho, Toyoake, Aichi 470-1192, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Ueda
authors.affiliation: Department of Neurology, Fujita Health University School of Medicine, 1-98 Kutsukake-cho, Toyoake, Aichi 470-1192, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Ito
authors.affiliation: Department of Neurology, Fujita Health University School of Medicine, 1-98 Kutsukake-cho, Toyoake, Aichi 470-1192, Japan.
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Mutoh
mesh_terms: D000107:Acetylation; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D007464:Clioquinol / Q000633:toxicity*; D019610:Cytoprotection; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D006877:Hydroxamic Acids / Q000633:toxicity*; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016716:PC12 Cells; D010766:Phosphorylation; D051381:Rats; D020917:Receptor, trkA / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014162:Transfection
chemical_list: D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006877:Hydroxamic Acids; D018696:Neuroprotective Agents; C012589:trichostatin A; D007464:Clioquinol; D020917:Receptor, trkA
keywords: Clioquinol; Deacetylation of histones; Histone deacetylase inhibitor; Subacute myeloopticoneuropathy