title: Tescalcin is a potential target of class I histone deacetylase inhibitors in neurons.
abstract: Class I histone deacetylase (HDAC) inhibitors are believed to have positive effects on neurite outgrowth, synaptic plasticity, and neurogenesis in adult brain. However, the downstream molecular targets of class I HDAC inhibitors in neurons are not clear. Although class I HDAC inhibitors are thought to broadly promote transcription of many neuronal genes through enhancement of histone acetylation, the affected gene set may include unidentified genes that are essential for neuronal survival and function. To identify novel genes that are targets of class I HDAC inhibitors, we used a microarray to screen transcripts from neuronal cultures and evaluated changes in protein and mRNA expression following treatment with four HDAC inhibitors. We identified tescalcin (Tesc) as the most strongly up-regulated gene following treatment with class I HDAC inhibitors in neurons. Moreover, hippocampal neurons overexpressing TESC showed a greater than 5-fold increase in the total length of neurites and number of branch points compared with controls. These findings highlight a potentially important role for TESC in mediating the neuroprotective effect of class I HDAC inhibitors. TESC may also be involved in the development of brain and neurodegenerative diseases through epigenetic mechanisms.
authors.affiliation: Department of Molecular and Cellular Physiology, Graduate School of Medicine, University of the Ryukyus, 903-0215 Okinawa, Japan; Department of Neuropsychiatry, Graduate School of Medicine, University of the Ryukyus, 903-0215 Okinawa, Japan.
authors.forename: Gakuya
authors.initials: G
authors.lastname: Takamatsu
authors.affiliation: Department of Molecular and Cellular Physiology, Graduate School of Medicine, University of the Ryukyus, 903-0215 Okinawa, Japan; Department of Neurosurgery, Graduate School of Medicine, University of the Ryukyus, 903-0215 Okinawa, Japan.
authors.forename: Chiaki
authors.initials: C
authors.lastname: Katagiri
authors.affiliation: Department of Molecular and Cellular Physiology, Graduate School of Medicine, University of the Ryukyus, 903-0215 Okinawa, Japan.
authors.forename: Tsumuraya
authors.initials: T
authors.lastname: Tomoyuki
authors.affiliation: Department of Molecular Anatomy, Graduate School of Medicine, University of the Ryukyus, 903-0215 Okinawa, Japan.
authors.forename: Chigusa
authors.initials: C
authors.lastname: Shimizu-Okabe
authors.affiliation: Department of Molecular and Cellular Physiology, Graduate School of Medicine, University of the Ryukyus, 903-0215 Okinawa, Japan.
authors.forename: Wakako
authors.initials: W
authors.lastname: Nakamura
authors.affiliation: Department of Molecular and Cellular Physiology, Graduate School of Medicine, University of the Ryukyus, 903-0215 Okinawa, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Nakamura-Higa
authors.affiliation: Department of Molecular and Cellular Physiology, Graduate School of Medicine, University of the Ryukyus, 903-0215 Okinawa, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Hayakawa
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Osaka Medical College, 569-8686 Osaka, Japan.
authors.forename: Shigeo
authors.initials: S
authors.lastname: Wakabayashi
authors.affiliation: Department of Neuropsychiatry, Graduate School of Medicine, University of the Ryukyus, 903-0215 Okinawa, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Kondo
authors.affiliation: Department of Molecular Anatomy, Graduate School of Medicine, University of the Ryukyus, 903-0215 Okinawa, Japan.
authors.forename: Chitoshi
authors.initials: C
authors.lastname: Takayama
authors.affiliation: Department of Molecular and Cellular Physiology, Graduate School of Medicine, University of the Ryukyus, 903-0215 Okinawa, Japan. Electronic address: masayuki@med.u-ryukyu.ac.jp.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Matsushita
mesh_terms: D000818:Animals; D019703:Calcineurin / Q000737:chemistry; D002118:Calcium / Q000737:chemistry; D002135:Calcium-Binding Proteins / Q000737:chemistry*; D016000:Cluster Analysis; D044127:Epigenesis, Genetic; D020869:Gene Expression Profiling; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology*; D056284:Histone Deacetylase 1 / Q000737:chemistry*; D056572:Histone Deacetylase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D006877:Hydroxamic Acids / Q000737:chemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016501:Neurites / Q000187:drug effects; D019636:Neurodegenerative Diseases / Q000378:metabolism; D055495:Neurogenesis / Q000187:drug effects; D009474:Neurons / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology; D020411:Oligonucleotide Array Sequence Analysis; D010957:Plasmids / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D012984:Software; D015854:Up-Regulation; D014635:Valproic Acid / Q000737:chemistry; D000077337:Vorinostat
chemical_list: D002135:Calcium-Binding Proteins; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D018696:Neuroprotective Agents; C420458:Tesc protein, mouse; D049452:Green Fluorescent Proteins; C012589:trichostatin A; D000077337:Vorinostat; D014635:Valproic Acid; D019703:Calcineurin; C484389:Hdac1 protein, mouse; D056284:Histone Deacetylase 1; D002118:Calcium
keywords: Calcineurin B homologous protein; Histone deacetylase; Suberoylanilide hydroxamic acid; Tescalcin; Trichostatin A; Valproate acid