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

Autor: Gakuya Takamatsu, Masayuki Matsushita, Wakako Nakamura, Mariko Nakamura-Higa, Chitoshi Takayama, Shigeo Wakabayashi, Tsumuraya Tomoyuki, Tsuyoshi Kondo, Chiaki Katagiri, Chigusa Shimizu-Okabe, Tomoko Hayakawa
Rok vydání: 2016
Předmět:
0301 basic medicine
Male
Neurite
Neurogenesis
Green Fluorescent Proteins
Biophysics
Histone Deacetylase 1
Biology
Hydroxamic Acids
Real-Time Polymerase Chain Reaction
Neuroprotection
Hippocampus
Biochemistry
Epigenesis
Genetic
03 medical and health sciences
Mice
0302 clinical medicine
Neurites
Animals
Cluster Analysis
Epigenetics
Molecular Biology
Oligonucleotide Array Sequence Analysis
Neurons
Histone deacetylase 5
Vorinostat
HDAC11
Calcineurin
Gene Expression Profiling
Valproic Acid
Calcium-Binding Proteins
Neurodegenerative Diseases
Cell Biology
Molecular biology
Cell biology
Up-Regulation
Histone Deacetylase Inhibitors
Mice
Inbred C57BL
030104 developmental biology
Histone
Neuroprotective Agents
biology.protein
Calcium
Histone deacetylase
030217 neurology & neurosurgery
Software
Plasmids
Zdroj: Biochemical and Biophysical Research Communications.
ISSN: 0006-291X
DOI: 10.1016/j.bbrc.2016.12.036
Popis: 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.
Databáze: OpenAIRE
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