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Upregulation of HIF-1α Via Activation of ERK and PI3K Pathway Mediated Protective Response to Microwave-Induced Mitochondrial Injury in Neuron-Like Cells

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Abstract

Microwave-induced learning and memory deficits in animal models have been gaining attention in recent years, largely because of increasing public concerns on growing environmental influences. The data from our group and others have showed that the injury of mitochondria, the major source of cellular adenosine triphosphate (ATP) in primary neurons, could be detected in the neuron cells of microwave-exposed rats. In this study, we provided some insights into the cellular and molecular mechanisms behind mitochondrial injury in PC12 cell-derived neuron-like cells. PC12 cell-derived neuron-like cells were exposed to 30 mW/cm2 microwave for 5 min, and damages of mitochondrial ultrastructure could be observed by using transmission electron microscopy. Impairments of mitochondrial function, indicated by decrease of ATP content, reduction of succinate dehydrogenase (SDH) and cytochrome c oxidase (COX) activities, decrease of mitochondrial membrane potential (MMP), and increase of reactive oxygen species (ROS) production, could be detected. We also found that hypoxia-inducible factor-1 (HIF-1α), a key regulator responsible for hypoxic response of the mammalian cells, was upregulated in microwave-exposed neuron-like cells. Furthermore, HIF-1α overexpression protected mitochondria from injury by increasing the ATP contents and MMP, while HIF-1α silence promoted microwave-induced mitochondrial damage. Finally, we demonstrated that both ERK and PI3K signaling activation are required in microwave-induced HIF-1α activation and protective response. In conclusion, we elucidated a regulatory connection between impairments of mitochondrial function and HIF-1α activation in microwave-exposed neuron-like cells. By modulating mitochondrial function and protecting neuron-like cells against microwave-induced mitochondrial injury, HIF-1α represents a promising therapeutic target for microwave radiation injury.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (No. 81372926) and Natural Science Foundation of Beijing (No. 7122127).

Competing Interests

The author(s) declare that they have no competing interests.

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Authors and Affiliations

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

    Li Zhao, Ya-Bing Gao, Shui-Ming Wang, Li-Feng Wang, Hong-Yan Zuo, Ji Dong, Xin-Ping Xu & Rui-Yun Peng

  2. Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing, 100850, People’s Republic of China

    Yue-Feng Yang

  3. Department of Radiation Protection and Health Physics, Beijing Institute of Radiation Medicine, Beijing, 100850, People’s Republic of China

    Zhen-Tao Su & Hong-Mei Zhou

  4. Department of Cognitive Sciences, Beijing Institute of Basic Medical Sciences, Beijing, 100850, People’s Republic of China

    Ling-Ling Zhu

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  1. Li Zhao
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Correspondence to Rui-Yun Peng.

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Li Zhao and Yue-Feng Yang contribute equally to this work.

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Zhao, L., Yang, YF., Gao, YB. et al. Upregulation of HIF-1α Via Activation of ERK and PI3K Pathway Mediated Protective Response to Microwave-Induced Mitochondrial Injury in Neuron-Like Cells. Mol Neurobiol 50, 1024–1034 (2014). https://doi.org/10.1007/s12035-014-8667-z

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