CDK5 Contributes to Neuronal Apoptosis via Promoting MEF2D Phosphorylation in Rat Model of Intracerebral Hemorrhage

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• 作者：Kaifu Ke (1) (2)
  Jiabing Shen (1) (2)
  Yan Song (1) (2)
  Maohong Cao (1)
  Hongjian Lu (3)
  Chun Liu (4)
  Jianhong Shen (1)
  Aihong Li (1)
  Jie Huang (1) (2)
  Haidan Ni (1) (2)
  Xiaomei Chen (5)
  Yonghua Liu (2) (6)
  
  1. Department of Neurology ; Affiliated Hospital of Nantong University ; Nantong ; 226001 ; Jiangsu Province ; China
  2. Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target ; Medical College of Nantong University ; Nantong ; 226001 ; Jiangsu Province ; China
  3. Department of Rehabilitation ; The Second People鈥檚 Hospital of Nantong ; Nantong ; 226002 ; Jiangsu Province ; China
  4. Laboratory Animal Center ; Nantong University ; Nantong ; 226001 ; Jiangsu Province ; China
  5. Shanghai Center for Plant Stress Biology ; Shanghai Institutes for Biological Sciences ; Chinese Academy of Sciences ; Shanghai ; 201602 ; China
  6. Department of Pathogen Biology ; Medical College ; Nantong University ; Nantong ; 226001 ; Jiangsu Province ; China
  
• 关键词：Hemorrhage ; CDK5 ; Apoptosis ; Neurons ; MEF2D
• 刊名：Journal of Molecular Neuroscience
• 出版年：2015
• 出版时间：May 2015
• 年：2015
• 卷：56
• 期：1
• 页码：48-59
• 全文大小：5,276 KB
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• 刊物主题：Neurosciences; Neurochemistry; Cell Biology; Proteomics; Neurology;
• 出版者：Springer US
• ISSN：1559-1166

文摘

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 ser444 residues. Thus, we speculated that CDK5 might exert an important function in the regulation of neuronal apoptosis following ICH.