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RKIP Regulates Neural Cell Apoptosis Induced by Exposure to Microwave Radiation Partly Through the MEK/ERK/CREB Pathway

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Abstract

In the present study, we investigated whether Raf-1 kinase inhibitory protein (RKIP) is important for neural cell apoptosis induced by microwave exposure and explored the role of MEK/ERK/CREB pathway regulated by RKIP in the apoptosis. Differentiated PC12 cells were exposed to continuous microwave radiation at 2.856 GHz for 5 min with average power density of 30 mW/cm2. RKIP sense and anti-sense recombinant plasmids were constructed and transfected into PC12 cells, respectively. Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) staining and caspase-3 activity assay were used to detect cell apoptosis. The results showed that RKIP was downregulated after microwave exposure while the MEK/ERK/CREB signaling pathway was activated excessively. Moreover, the ratio of Bcl-2/Bax decreased, activity of caspase-3 increased, and thus apoptotic DNA fragmentation increased. RKIP overexpression significantly inhibited the phosphorylation of MEK, ERK, and CREB, while RKIP downregulation had the reverse effect. Furthermore, U0126 was found to antagonize the changes caused by RKIP downregulation after exposure to radiation. In conclusion, RKIP plays an important role in the neural cell apoptosis induced by microwave radiation, and the regulation of cell apoptosis by RKIP is partly through the MEK/ERK/CREB pathway. This suggests that RKIP may act as a key regulator of neuronal damage caused by microwave radiation.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (30770527, 81102101), the Military Medical Fund (CWS11J073), and the Major National Science and Technology Program of China (2008ZXJ09004-019). We sincerely thank professor Fu Hanjiang for providing the plasmid vector and Dr. Zhang Zhiyi, Zhou Peilan, Xu Chengwang, and Zhou Hongmei for their excellent technical assistance.

Conflict of Interest

All authors declared that there are no conflict of interest.

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Authors and Affiliations

  1. Department of Experimental Pathology, Beijing Institute of Radiation Medicine, 27, Taiping Road,, Haidian District, Beijing, 100850, China

    Hongyan Zuo, Dewen Wang, Ruiyun Peng, Shuiming Wang, Yabing Gao, Xinping Xu, Li Zhao & Shaoxia Wang

  2. High Magnetic Field Laboratory, Hefei Material Research Institute, Chinese Academy of Science, 350, Shushanhu Road,, Shushan District, Hefei, 230031, China

    Tao Lin

  3. Department of Radiation Protection and Health Physics, Beijing Institute of Radiation Medicine, 27, Taiping Road,, Haidian District, Beijing, 100850, China

    Zhentao Su

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  1. Hongyan Zuo
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Correspondence to Dewen Wang or Ruiyun Peng.

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Hongyan Zuo and Tao Lin contributed equally to this work.

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Zuo, H., Lin, T., Wang, D. et al. RKIP Regulates Neural Cell Apoptosis Induced by Exposure to Microwave Radiation Partly Through the MEK/ERK/CREB Pathway. Mol Neurobiol 51, 1520–1529 (2015). https://doi.org/10.1007/s12035-014-8831-5

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