2003 Fiscal Year Final Research Report Summary
Mitochondrial dysfunction mediated by the activation of glucocorticoid receptor
| Project/Area Number |
14570601
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | The University of Tokushima |
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Principal Investigator |
TAKAO Mitsuki University of Tokushima, Tokushima University Hospital, Assistant Professor, 医学部・歯学部附属病院, 講師 (80294726)
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| Co-Investigator(Kenkyū-buntansha) |
AKAIKE Masashi University of Tokushima, Tokushima University Hospital, Research Assistant, 医学部・歯学部附属病院, 助手 (90271080)
AZUMA Hiroyuki University of Tokushima, School of Medicine, Assocoate Professor, 医学部, 助教授 (10241275)
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| Project Period (FY) |
2002 – 2003
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| Keywords | reactive oxygen species / superoxide dismutase / mitochondrial dysfunction / apoptosis |
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| Research Abstract |
Corticosteroid myopathy is a major clinical problem in patients undergoing chronic corticosteroid treatment and shows insidious and progressive muscle atrophy. Although several mechanisms underlying the pathophysiology of muscle injury have been reported, precise pathogenetic mechanism is still uncertain. Recently, we found the significant mitochondrial dysfunction in patients administered with corticosteroids compared with those in healthy controls or patients not receiving corticosteroids. The diseased muscle biopsied showed significant oxidative damage in patients with corticosteroid administration. Our results suggest that mitochondrial dysfunction and oxidative damage play an important role the development of corticosteroid myopathy.
In the sresent study, we analyzed effects of corticosteroid on mitochondrial membrane potentials (ΔΨm), generation of reactive oxygen species (ROS) and apoptosis in human rhabdomyosarcome cell line, RD and a dopaminergic neuroblastoma cell line, SH-SY5Y. The cell lines were cultured in the presence or absence of dexamethasone and superoxide dismutase (SOD) up to one week. Dexamethasone treatment showed acute effect of increasing ΔΨm, ROS generation and apoptosis in proliferating RD cells. Treatment with SOD attenuated ROS generation and apoptosis but not ΔΨm. The increase in AWm seems to be the primary effect of dexamethasone on proliferating RD cells, which is probably mediated by mitochondrial transcription. In differentiated RD cells but not in differentiated SH-SY5Y cells, dexamethasone treatment showed delayed effect of interfering the ΔΨm and increasing ROS generation and apoptosis. Since these changes disappeared in the presence of SOD, dexamethasone seems to primarily induces ROS generation, resulting in apoptosis. We speculate this mechanism to be a pathophysiological model of corticosteroid myopathy.
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Research Products
(12 results)
