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RETRACTED ARTICLE: The Crucial Role of Cyclin-Dependent Kinase-5-Ataxia-Telangiectasia Mutated Axis in ICH-Induced Neuronal Injury of Rat Model

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This article was retracted on 01 July 2017

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.

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Acknowledgments

This study is supported by Chong Qing Natural Science Foundation (cstc2015jcyjA0526). We greatly thank other members in our lab for valuable suggestions and writing.

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Authors and Affiliations

  1. Intensive Care Unit, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China

    Jing Wu

  2. Institute of Molecular Biology, Chongqing Medical University, Chongqing, 400016, China

    Xin Zhang

  3. Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China

    Yi Yan, Zhaohua Tang, Xiaochuan Sun, Gang Huo & Zhengbu Liao

Authors
  1. Jing Wu
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  2. Xin Zhang
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  3. Yi Yan
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  4. Zhaohua Tang
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  5. Xiaochuan Sun
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  6. Gang Huo
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  7. Zhengbu Liao
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Corresponding author

Correspondence to Zhengbu Liao.

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Disclosure Statement

The authors state that there are no conflicts of interest to disclose.

Additional information

This article has been retracted at the request of the Editor-in-Chief and the Publisher per the Committee on Publication Ethics guidelines. There is strong reason to believe that the peer review process was compromised. As such the validity of the content of this article cannot be verified.

An erratum to this article is available at http://dx.doi.org/10.1007/s12035-017-0651-y.

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Wu, J., Zhang, X., Yan, Y. et al. RETRACTED ARTICLE: The Crucial Role of Cyclin-Dependent Kinase-5-Ataxia-Telangiectasia Mutated Axis in ICH-Induced Neuronal Injury of Rat Model. Mol Neurobiol 53, 6301–6308 (2016). https://doi.org/10.1007/s12035-015-9524-4

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  • DOI: https://doi.org/10.1007/s12035-015-9524-4

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