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Nuclear translocation of anamorsin during drug-induced dopaminergic neurodegeneration in culture and in rat brain

  • Basic Neurosciences, Genetics and Immunology - Original Article
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Abstract

Anamorsin, also called cytokine-induced apoptosis inhibitor 1 (CIAPIN1), was recently identified to confer resistance to apoptosis induced by growth factor deprivation and to be indispensible for hematopoiesis. Recently, it was demonstrated that anamorsin is also widely distributed in both fetal and adult tissues. In this study, we evaluated the tissue distribution of anamorsin in the central nervous system (CNS) during development. In situ hybridization and immunoblot analyses revealed that anamorsin mRNA and protein were both highly and widely expressed in various regions of the CNS, including the cerebral cortex, hippocampus, midbrain, cerebellum, medulla, and spinal cord. Based on these findings, we examined its cellular localization during drug-induced neurodegeneration in MN9D dopaminergic cells. Both immunocytochemical localization and immunoblot analyses indicated that cytosolic anamorsin was translocated into the nucleus in a time-dependent manner following treatment with a reactive oxygen species (ROS)-inducing drug, 6-hydroxydopamine (6-OHDA). Treatment of cells with the apoptosis-inducing reagent, staurosporine, did not appear to cause translocation of anamorsin into the nucleus. When cells were treated with the nuclear export inhibitor, Leptomycin B, alone or with 6-OHDA, nuclear anamorsin levels increased, indicating that nuclear influx and efflux of anamorsin are regulated by 6-OHDA treatment. In rat brain injected with 6-OHDA, nuclear translocation of anamorsin was identified in certain tyrosine hydroxylase (TH)-positive neurons as well as TH-negative cells. Furthermore, treatment of MN9D cells with hydrogen peroxide or ROS-inducing trace metals caused nuclear translocation of anamorsin. Taken together, our data indicate that nuclear translocation of anamorsin is a ROS-dependent event and may participate in the regulation of transcription of critical molecules during dopaminergic neurodegeneration.

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Acknowledgments

The authors thank Dr. A. Heller for allowing us to use the MN9D cell line. We also greatly appreciate critical suggestions made by Dr. Moussa B.H. Youdim. We would like to dedicate much of our work to Dr. Youdim on his 70th birthday. This work was supported by a grant from Ministry of Health and Welfare (A090063), and, in part, by the Brain Research Center, World Class University (WCU, R33-2208-10014) and KOSEF through SRC (R11-2008-036).

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Authors and Affiliations

  1. Department of Biology, Yonsei University College of Life Science and Biotechnology, 134 Shincheon-dong Seodaemoon-gu, Seoul, 120-749, Korea

    Kyung-Ah Park, Nuri Yun, Dong-Ik Shin & Young J. Oh

  2. Department of Anatomy and Brain Korea 21 Biomedical Science Program, Korea University College of Medicine, Seoul, 136-705, Korea

    So Yoen Choi, Hyun Kim & Won-Ki Kim

  3. Department of Hematology and Oncology, Osaka University Graduate School of Medicine, Osaka, 565-0871, Japan

    Yuzuru Kanakura & Hirohiko Shibayama

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  1. Kyung-Ah Park
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  2. Nuri Yun
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Correspondence to Young J. Oh.

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Park, KA., Yun, N., Shin, DI. et al. Nuclear translocation of anamorsin during drug-induced dopaminergic neurodegeneration in culture and in rat brain. J Neural Transm 118, 433–444 (2011). https://doi.org/10.1007/s00702-010-0490-8

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  • DOI: https://doi.org/10.1007/s00702-010-0490-8

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