TY - JOUR
T1 - Nuclear translocation of anamorsin during drug-induced dopaminergic neurodegeneration in culture and in rat brain.
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 J.
N1 - Funding Information:
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).
PY - 2011/3
Y1 - 2011/3
N2 - 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.
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.
UR - http://www.scopus.com/inward/record.url?scp=80051647343&partnerID=8YFLogxK
U2 - 10.1007/s00702-010-0490-8
DO - 10.1007/s00702-010-0490-8
M3 - Article
C2 - 20924620
AN - SCOPUS:80051647343
SN - 0300-9564
VL - 118
SP - 433
EP - 444
JO - Journal of neural transmission (Vienna, Austria : 1996)
JF - Journal of neural transmission (Vienna, Austria : 1996)
IS - 3
ER -
