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Phospho-Rb Mediating Cell Cycle Reentry Induces Early Apoptosis Following Oxygen–Glucose Deprivation in Rat Cortical Neurons

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Abstract

The aim of this study was to investigate the relationship between cell cycle reentry and apoptosis in cultured cortical neurons following oxygen–glucose deprivation (OGD). We found that the percentage of neurons with BrdU uptake, TUNEL staining, and colocalized BrdU uptake and TUNEL staining was increased relative to control 6, 12 and 24 h after 1 h of OGD. The number of neurons with colocalized BrdU and TUNEL staining was decreased relative to the number of TUNEL-positive neurons at 24 h. The expression of phosphorylated retinoblastoma protein (phospho-Rb) was significantly increased 6, 12 and 24 h after OGD, parallel with the changes in BrdU uptake. Phospho-Rb and TUNEL staining were colocalized in neurons 6 and 12 h after OGD. This colocalization was strikingly decreased 24 h after OGD. Treatment with the cyclin-dependent kinase inhibitor roscovitine (100 μM) decreased the expression of phospho-Rb and reduced neuronal apoptosis in vitro. These results demonstrated that attempted cell cycle reentry with phosphorylation of Rb induce early apoptosis in neurons after OGD and there must be other mechanisms involved in the later stages of neuronal apoptosis besides cell cycle reentry. Phosphoralated Rb may be an important factor which closely associates aberrant cell cycle reentry with the early stages of neuronal apoptosis following ischemia/hypoxia in vitro, and pharmacological interventions for neuroprotection may be useful directed at this keypoint.

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Acknowledgments

This work was supported by National Science Fund for Distinguished Young Scholars (30725019) and the National Natural Science Foundation of China (30900447).

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Authors and Affiliations

  1. Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, 430060, People’s Republic of China

    Ying Yu, Zhao-Hui Zhang & Ke Zhou

  2. Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China

    Zhi-Yuan Yu, Xiang Luo & Wei Wang

  3. Department of Neurology, Zhongda Hospital and the Institution of Cerebral Vascular Disease of Southeast University, Nanjing, 210009, People’s Republic of China

    Qing-Guo Ren

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  1. Ying Yu
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  2. Qing-Guo Ren
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  3. Zhao-Hui Zhang
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  4. Ke Zhou
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  5. Zhi-Yuan Yu
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  6. Xiang Luo
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  7. Wei Wang
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Corresponding author

Correspondence to Wei Wang.

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Ying Yu and Qing-Guo Ren contributed equally to this work.

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Yu, Y., Ren, QG., Zhang, ZH. et al. Phospho-Rb Mediating Cell Cycle Reentry Induces Early Apoptosis Following Oxygen–Glucose Deprivation in Rat Cortical Neurons. Neurochem Res 37, 503–511 (2012). https://doi.org/10.1007/s11064-011-0636-6

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  • DOI: https://doi.org/10.1007/s11064-011-0636-6

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