| Project/Area Number |
12670606
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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 |
MITSUI Takao The University of Tokushima, Tokushima University Hospital, Assistant Professor, 医学部・附属病院, 講師 (80294726)
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| Co-Investigator(Kenkyū-buntansha) |
AZUMA Hiroyuki The University of Tokukshima, School of Medicine, Associate Professor, 医学部, 助教授 (10241275)
AKAIKE Masashi The University of Tokushima, Tokushima University Hospital, Research Associate, 医学部・附属病院, 助手 (90271080)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2001: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2000: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | Mitochondrial damage / Corticosteroid myopathy / Mitochondrial encephalomyopathy / Reactive oxigen species |
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| Research Abstract |
Corticosteroid myopathy is a major clinical problem in patients undergoing chronic corticosteroid treatment and shows insideous and progressive muscle atrophy in proximal limbs. Although several mechanisms underlying the pathophysiology of muscle injury have been postulated, precise pathogenesis is still not clear.
We evaluated the mitochondrial functions in patients administered with conticosteroids compared with those in healthy controls or patients not receiving corticosteroids. The serum levels and total production of lactate were investigated by an aerobic exercise test using a bicycle ergometer. Mitochondrial respiratory activities and oxidative damage in biopsied skeletal muscles were also studied. The results of aerobic exercise tests revealed a significant overproduction of lactate in patients treated with corticosteroids (p<0.005), which was positively correlated with total corticosteroid doses administered (p<0.0001). In these patients, mitochondrial enzyme activity in complex I was significantly decreased (p<0.05) and oxidative damage of biopsied skeletal muscle was remarkable both in mitochondrial and nuclear DNAs (p<0.001).
The corticosteroid-induced mitochondrial damage was further studied in a cultured human muscle cell line, RD cell. RD cells were cultured in a medium containing 10^5-10^7M dexamethasone for 3 hours to 7 days. Reactive oxygen species and apoptosis were analyzed by flowcytometry using DCFHDA and Annexin V/PI, respectively. The production of reactive oxygen species was progressively increased form 3 hours to 7 days and apoptosis was prominent from 2 to 7 days. SOD (100 u/ml) decreased the production of reactive oxygen species and the apoptotic change.
The results suggest that chronic corticosteroid administration induces oxidative damage-mediated mitochondrial dysfunction in skeletal muscles, which may be the pathogenesis, at least in part, of corticosteroid-induced myopathy.
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