title: The Crucial Role of Cyclin-Dependent Kinase-5-Ataxia-Telangiectasia Mutated Axis in ICH-Induced Neuronal Injury of Rat Model.
abstract: Cyclin-dependent kinase 5 (CDK5) and ataxia-telangiectasia mutated (ATM) are involved in normal human neurodevelopment and serves as a switch between neuronal survival and death. However, the molecular mechanisms underlying CDK5-ATM-induced neuronal injury caused by intracerebral hemorrhage (ICH) remain unclear. In this work, we used rat ICH models and thrombin-induced cell models to investigate the potential role of CDK5-ATM signals. Our findings revealed that CDK5 protein levels and kinase activities (p-histone H1 expression) were enforced in hematoma-surrounding neuron tissues following ICH. Besides, the expression of p25, p-ATM, and active caspase-3 protein was also upregulated after ICH. According to in vitro assays, the expression of CDK5, p-ATM, and active caspase-3 was all upregulated in cell viability-decreasing ICH cell models. However, blocking of either CDK5 or ATM suppressed the phosphorylation of ATM and the expression of active caspase-3, and attenuated the inhibition of neuronal survival. When p35/p25 was silenced, CDK5-ATM pathway was further inhibited, and cell viability was obviously ameliorated. In conclusion, this work suggested that ATM could be phosphorylated by CDK5 to induce the active caspase-3 and neuronal injury when intracerebral hemorrhage or ischemia occurred. Thus, the CDK5-AMT signal pathway has an important role in ICH process and may be a therapeutic target to prevent brain injury.
authors.affiliation: Intensive Care Unit, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.affiliation: Institute of Molecular Biology, Chongqing Medical University, Chongqing, 400016, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Yan
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
authors.forename: Zhaohua
authors.initials: Z
authors.lastname: Tang
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
authors.forename: Xiaochuan
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Huo
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China. liaozhengbu163@163.com.
authors.forename: Zhengbu
authors.initials: Z
authors.lastname: Liao
keywords: ATM; CDK5; ICH; Rat