2002 Fiscal Year Final Research Report Summary
Molecular Basis of Mitochondrial Myopathy and Animal Models Related to the Energy Abnormality
| Project/Area Number |
13670853
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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 |
Pediatrics
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| Research Institution | KURUME UNIVERSITY |
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Principal Investigator |
KOGA Yasutoshi Department of Pediatrics and Child Health, Kurume University School of Medicine, Associate Professor, 医学部, 助教授 (00225400)
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| Co-Investigator(Kenkyū-buntansha) |
AKITA Yukihiro Department of Pediatrics and Child Health, Kurume University School of Medicine, assistant, 医学部, 助手 (20330821)
FUKIYAMA Ryo Department of Pediatrics and Child Health, Kurume University School of Medicine, assistant, 医学部, 助手 (40289434)
IWANAGA Rikako Department of Pediatrics and Child Health, Kurume University School of Medicine, assistant, 医学部, 助手 (20258396)
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| Project Period (FY) |
2001 – 2002
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| Keywords | Mitochondrial stroke / endothelial dyfunction / Nitric oxide / Mitochondrial disease / mitochondrial tRNA mutation / L-arginine / RNA19 / Klotho Knockout mouse |
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| Research Abstract |
Mitochondrial myopathy is a mutisystem disorders characterized by dysfunctions of mitochondrial energy metabolism. To investigate and clarify the molecular basis of mitochondrial myopathy, the creation of animal models is essential. In 1997, Klotho gene knockout mice have been developed as a model of human aging. However, there are no reports to investigate the molecular mechanism of abnormality in the mitochondrial energy metabolism in Klotho gene knockout mice. In this project, we planned to investigate the mitochondrial energy metabolism in Klotho gene knockout mice including mitochondrial respiratory chain enzyme, cytochrome contents, oxograph, uptake of neurotransmitters in synaptosome, muscle histochemistry and mitochondrial DNA abnormalities to evaluate the relationship between aging and mitochondrial energy metabolism.
MELAS, is a maternally-inherited mitochondrial multisystem disorder, characterized early onset stroke before age 20. Mitochondrial angiopathy demonstrating degene
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rative change with increased abnormal mitochondria in the endothelial cells of intramuscular small arteries and arterioles has been reported in many MELAS patients. However, the primary cause for stroke-like episodes in young MELAS patients - whether mitochondrial cytopathy, angiopathy, or both - remains controversial. Based on a hypothesis that stroke-like episodes in MELAS are caused by segmental impairment of vasodilation in intracerebral arteries, we administered L-arginine to MELAS in the acute phase of stroke. We reported that L-arginine therapy quickly improved the symptoms of stroke in MELAS, improved the microcirculation, and also reduced tissue injury from ischemia. We demonstrated the pharmacological effects of L-arginine on the acute phase of stroke-like episodes to determine whether the plasma concentrations of biological parameters including L-arginine, NOx, or ADMA, the important regulatory factors to the endothelial functions, are changed in patients with MELAS compared with normal subjects. L-arginine therapy improved the microcirculation to reduce tissue injury from ischemia, and therefore constitutes a new potential therapy for use in the acute phase of strokelike episodes in MELAS. Less
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Research Products
(12 results)
