title: CDK5 contributes to neuronal apoptosis via promoting MEF2D phosphorylation in rat model of intracerebral hemorrhage.
abstract: Cyclin-dependent kinase-5 (CDK5), a serine/threonine kinase which can be activated by its neuron-specific activator p35, or its truncated form p25, plays an important role in a variety of neuronal events, including neuronal migration, synaptic transmission, and neuronal death. Accumulating evidence has shown that abnormal activation of CDK5 was a critical neuronal pro-death signal in central nervous system (CNS) diseases. However, it remains unclear how CDK5 functions upon neuronal apoptosis following intracerebral hemorrhage (ICH). In the present study, we established ICH models by injecting autologous whole blood into the right basal ganglia of adult rats and assessed their neurological deficits by behavioral tests. CDK5 protein levels and kinase activities were upregulated adjacent to the hematoma following ICH. Immunofluorescent staining showed CDK5 was mainly localized in neurons, rather than in astrocytes or oligodendrocytes. Furthermore, active caspase-3, an apoptotic marker, showed a temporally parallel expression with the protein levels/kinase activities of CDK5 following ICH. Meantime, myocyte enhancer factor 2D (MEF2D), a pro-survival transcription factor which could be phosphorylated inactivation by CDK5, also exhibited high phosphorylation levels following ICH. In vitro, we obtained a consistent upregulation of CDK5 kinase activity in primary cortical neurons after thrombin treatment. Knocking down CDK5 kinase activity suppressed neuronal apoptosis and coupled with reduced MEF2D phosphorylation at ser(444) residues. Thus, we speculated that CDK5 might exert an important function in the regulation of neuronal apoptosis following ICH.
authors.affiliation: Department of Neurology, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu Province, China.
authors.forename: Kaifu
authors.initials: K
authors.lastname: Ke
authors.forename: Jiabing
authors.initials: J
authors.lastname: Shen
authors.forename: Yan
authors.initials: Y
authors.lastname: Song
authors.forename: Maohong
authors.initials: M
authors.lastname: Cao
authors.forename: Hongjian
authors.initials: H
authors.lastname: Lu
authors.forename: Chun
authors.initials: C
authors.lastname: Liu
authors.forename: Jianhong
authors.initials: J
authors.lastname: Shen
authors.forename: Aihong
authors.initials: A
authors.lastname: Li
authors.forename: Jie
authors.initials: J
authors.lastname: Huang
authors.forename: Haidan
authors.initials: H
authors.lastname: Ni
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Chen
authors.forename: Yonghua
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis; D001253:Astrocytes / Q000378:metabolism; D002543:Cerebral Hemorrhage / Q000378:metabolism*; D051360:Cyclin-Dependent Kinase 5 / Q000235:genetics / Q000378:metabolism*; D064326:MEF2 Transcription Factors / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000378:metabolism*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D064326:MEF2 Transcription Factors; C578045:MEF2D protein, rat; D051360:Cyclin-Dependent Kinase 5; C495907:Cdk5 protein, rat