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

Kyung Ah Park, Nuri Yun, Dong Ik Shin, So Yoen Choi, Hyun Kim, Won Ki Kim, Yuzuru Kanakura, Hirohiko Shibayama, Young Jun Oh

Research output: Contribution to journalArticle

10 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)433-444
Number of pages12
JournalJournal of neural transmission (Vienna, Austria : 1996)
Volume118
Issue number3
DOIs
Publication statusPublished - 2011 Mar 1

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Dopamine Agents
Oxidopamine
Brain
Reactive Oxygen Species
Tyrosine 3-Monooxygenase
Apoptosis
Central Nervous System
Staurosporine
Cell Nucleus Active Transport
Hematopoiesis
Tissue Distribution
Mesencephalon
Pharmaceutical Preparations
Cerebral Cortex
Cerebellum
Hydrogen Peroxide
In Situ Hybridization
Hippocampus
Spinal Cord
Intercellular Signaling Peptides and Proteins

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology
  • Psychiatry and Mental health
  • Biological Psychiatry

Cite this

Park, Kyung Ah ; Yun, Nuri ; Shin, Dong Ik ; Choi, So Yoen ; Kim, Hyun ; Kim, Won Ki ; Kanakura, Yuzuru ; Shibayama, Hirohiko ; Oh, Young Jun. / Nuclear translocation of anamorsin during drug-induced dopaminergic neurodegeneration in culture and in rat brain. In: Journal of neural transmission (Vienna, Austria : 1996). 2011 ; Vol. 118, No. 3. pp. 433-444.
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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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Nuclear translocation of anamorsin during drug-induced dopaminergic neurodegeneration in culture and in rat brain. / Park, Kyung Ah; Yun, Nuri; Shin, Dong Ik; Choi, So Yoen; Kim, Hyun; Kim, Won Ki; Kanakura, Yuzuru; Shibayama, Hirohiko; Oh, Young Jun.

In: Journal of neural transmission (Vienna, Austria : 1996), Vol. 118, No. 3, 01.03.2011, p. 433-444.

Research output: Contribution to journalArticle

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AU - Park, Kyung Ah

AU - Yun, Nuri

AU - Shin, Dong Ik

AU - Choi, So Yoen

AU - Kim, Hyun

AU - Kim, Won Ki

AU - Kanakura, Yuzuru

AU - Shibayama, Hirohiko

AU - Oh, Young Jun

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AB - 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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