Tescalcin is a potential target of class I histone deacetylase inhibitors in neurons

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...

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Published in:Biochemical and biophysical research communications 2017-01, Vol.482 (4), p.1327-1333
Main Authors: Takamatsu, Gakuya, Katagiri, Chiaki, Tomoyuki, Tsumuraya, Shimizu-Okabe, Chigusa, Nakamura, Wakako, Nakamura-Higa, Mariko, Hayakawa, Tomoko, Wakabayashi, Shigeo, Kondo, Tsuyoshi, Takayama, Chitoshi, Matsushita, Masayuki
Format: Article
Language:English
Subjects:
Animals
Calcineurin - chemistry
Calcineurin B homologous protein
Calcium - chemistry
Calcium-Binding Proteins - chemistry
Cluster Analysis
Epigenesis, Genetic
Gene Expression Profiling
Green Fluorescent Proteins - metabolism
Hippocampus - cytology
Histone deacetylase
Histone Deacetylase 1 - chemistry
Histone Deacetylase Inhibitors - chemistry
Histone Deacetylase Inhibitors - pharmacology
Hydroxamic Acids - chemistry
Male
Mice
Mice, Inbred C57BL
Neurites - drug effects
Neurodegenerative Diseases - metabolism
Neurogenesis - drug effects
Neurons - metabolism
Neuroprotective Agents - pharmacology
Oligonucleotide Array Sequence Analysis
Plasmids - metabolism
Real-Time Polymerase Chain Reaction
Software
Suberoylanilide hydroxamic acid
Tescalcin
Trichostatin A
Up-Regulation
Valproate acid
Valproic Acid - chemistry
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Summary: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. •We found tescalcin (Tesc) as a potential target gene of class I HDAC inhibitors in neuron.•Class I HDAC inhibitors strongly induced TESC expression in hippocampal neurons.•TESC overexpression promoted neurite outgrowth and branching in neurons.•A Ca2+-unbound EF-hand mutant of tescalcin slightly reduced neurite outgrowth.•A potentially key role for TESC in class I HDAC inhibitor treatment is predicted.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2016.12.036