title: Intracellular translocation of histone deacetylase 5 regulates neuronal cell apoptosis.
abstract: Histone deacetylase 5 (HDAC5) undergoes signal-dependent shuttling between the nucleus and cytoplasm, which is regulated in part by calcium/calmodulin-dependent kinase (CaMK)-mediated phosphorylation. Here, we report that HDAC5 regulates the survival of cortical neurons in pathological conditions. HDAC5 was evenly localized to the nucleus and cytoplasm in cultured cortical neurons. However, in response to 50μM NMDA conditions that induced neuronal cell apoptosis, nuclear-distributed HDAC5 was rapidly phosphorylated and translocated into cytoplasm of the cultured cortical neurons. Treatment with a CaMKII inhibitor KN93 suppressed HDAC5 phosphorylation and nuclear translocation induced by NMDA, whereas constitutively active CaMKIIα (T286D) stimulated HDAC5 nuclear export. Importantly, we showed that ectopic expression of nuclear-localized HDAC5 in cortical neurons suppressed NMDA-induced apoptosis. Finally, inactivation of HDAC5 by treatment with the class II-specific HDAC inhibitor trichostatin A (TSA) promoted NMDA-induced neuronal cell apoptosis. Altogether, these data identify HDAC5 and its intracellular translocation as key effectors of multiple pathways that regulate neuronal cell apoptosis.
authors: Department of Developmental Biology, Key Lab of Cell Biology, Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, 92 Beier Road, Heping District, Shenyang 110001, China.
authors: Jia-Yi
authors: JY
authors: Wei
authors: Department of Developmental Biology, Key Lab of Cell Biology, Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, 92 Beier Road, Heping District, Shenyang 110001, China.
authors: Qiu-Nan
authors: QN
authors: Lu
authors: Department of Developmental Biology, Key Lab of Cell Biology, Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, 92 Beier Road, Heping District, Shenyang 110001, China.
authors: Wan-Ming
authors: WM
authors: Li
authors: Department of Developmental Biology, Key Lab of Cell Biology, Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, 92 Beier Road, Heping District, Shenyang 110001, China. Electronic address: hweicmu@163.com.
authors: Wei
authors: W
authors: He
mesh_terms: D000107:Acetylation; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001596:Benzylamines / Q000494:pharmacology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000201:enzymology; D004789:Enzyme Activation; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006655:Histone Deacetylases / Q000378:metabolism*; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*; D010766:Phosphorylation; D021381:Protein Transport; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000494:pharmacology; D000096926:Benzenesulfonamides
chemical_list: D001596:Benzylamines; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases; D016202:N-Methylaspartate; D013449:Sulfonamides; C072105:KN 93; D000096926:Benzenesulfonamides; C498619:Hdac5 protein, rat
keywords: Apoptosis; CaMKII; HDAC5; Histone acetylation; NMDA; Neuron