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Increased Membrane/Nuclear Translocation and Phosphorylation of p90 KD Ribosomal S6 Kinase in the Brain of Hypoxic Preconditioned Mice

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Abstract

Our previous studies have demonstrated that hypoxic precondition (HPC) increased membrane translocation of protein kinase C isoforms and decreased phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) in the brain of mice. The goal of this study was to determine the involvement of p90 KD ribosomal S6 kinase (RSK) in cerebral HPC of mice. Using Western-blot analysis, we found that the levels of membrane/nuclear translocation, but not protein expression of RSK increased significantly in the frontal cortex and hippocampus of HPC mice. In addition, we found that the phosphorylation levels of RSK at the Ser227 site (a PDK1 phosphorylation site), but not at the Thr359/Ser363 sites (ERK1/2 phosphorylated sites) increased significantly in the brain of HPC mice. Similar results were confirmed by an immunostaining study of total RSK and phospho-Ser227 RSK. To further define the cellular populations to express phospho-Ser227 RSK, we found that the expression of phospho-Ser227 RSK co-localized with neurogranin, a neuron-specific marker, in cortex and hippocampus of HPC mice by using double-labeled immunofluorescent staining method. These results suggest that increased RSK membrane/nuclear translocation and PDK1 mediated neuron-specific phosphorylation of RSK at Ser227 might be involved in the development of cerebral HPC of mice.

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Acknowledgments

This work was supported by the following grants: National Natural Science Foundation of China (30470650 and 30670782), Beijing Natural Science Foundation (07E0029), China 973 Program (2006CB504100), and NIH DE 15814. The authors thank Steve Schuenke for editorial assistance.

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Authors and Affiliations

  1. Department of Neurobiology, Beijing Key Laboratory for Neural Regeneration and Repairing, Institute for Biomedical Science of Pain, Capital Medical University, #10 You An Men Wai Xi Tou Tiao, Beijing, 100069, Peoples’ Republic of China

    Zhifeng Qi, Xiangning Bu, Ping Huang, Nan Zhang, Song Han & Junfa Li

  2. Division of Neurosurgery, Department of Surgery, Neuroscience and Cell Biology, The University of Texas Medical Branch, 301 University Boulevard, Galveston, TX, 77555-0517, USA

    Li Fang

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  1. Zhifeng Qi
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Correspondence to Junfa Li.

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Qi, Z., Bu, X., Huang, P. et al. Increased Membrane/Nuclear Translocation and Phosphorylation of p90 KD Ribosomal S6 Kinase in the Brain of Hypoxic Preconditioned Mice. Neurochem Res 32, 1450–1459 (2007). https://doi.org/10.1007/s11064-007-9331-z

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  • DOI: https://doi.org/10.1007/s11064-007-9331-z

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