Functional integrity of mitochondrial genomes in human platelets and autopsied brain tissues from elderly patients with Alzheimer's disease
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概要
- 論文の詳細を見る
To determine whether pathogenic mutations in mtDNA are involved in phenotypic expression of Alzheimer's disease (AD), the transfer of mtDNA from elderly patients with AD into mtDNA-less (ρ^0) HeLa cells was carried out by fusion of platelets or synaptosomal fractions of autopsied brain tissues with ρ^0 HeLa cells. The results showed that mtDNA in postmortem brain tissue survives for a long time without degradation and could be rescued in ρ^0 HeLa cells. Next, the cybrid clones repopulated with exogenously imported mtDNA from patients with AD were used for examination of respiratory enzyme activity and transfer of mtDNA with the pathogenic mutations that induce mitochondrial dysfunction. The presence of the mutated mtDNA was restricted to brain tissues and their cybrid clones that formed with synaptosomes as mtDNA donors, whereas no cybrid clones that isolated with platelets as mtDNA donors had detectable mutated mtDNA. However, biochemical analyses showed that all cybrid clones with mtDNA imported from platelets or brain tissues of patients with AD restored mitochondrial respiration activity to almost the same levels as those of cybrid clones with mtDNA from age-matched normal controls, suggesting functional integrity of mtDNA in both platelets and brain tissues of elderly patients with AD. These observations warrant the reassessment of the conventional concept that the accumulation of pathogenic mutations in mtDNA throughout the aging process is responsible for the decrease of mitochondrial respiration capacity with age and with the development of age-associated neurodegenerative diseases.
- 日本医科大学の論文
- 2000-03-25
著者
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Ohta Shigeo
Department of Biochemistry and Cell Biology, Institute of Development and Aging Science, Graduate Sc
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Ohta Shigeo
Department Of Biochemistry And Cell Biology Institute Of Development And Aging Science Graduate Scho
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Ohta Shigeo
Department Of Biochemistry And Cell Biology Institute Of Gerontology Nippon Medical School
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Kuno Shinya
Institute Of Health & Sport Sciences University Of Tsukuba
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Kuno Shinya
Institute Of Health And Sport Sciences University Of Tsukuba:center For Tsukuba Advanced Research Al
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Kagawa Yasuo
Women's University Of Nutrition
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Ito Sayaka
Institute Of Biological Sciences University Of Tsukuba
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MIZUSAWA Hidehiro
Department of Neurology and Neurological Science, Tokyo Medical and Dental University
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HAYASHI Junichi
Institute of Biological Sciences, University of Tsukaba.
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NISHIMAKI KIYOMI
Department of Biochemistry and Cell Biology, Institute of Development and Aging Sciences, Graduate S
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Nishimaki Kiyomi
Department Of Biochemistry And Cell Biology Institute Of Gerontology Nippon Medical School
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Nishimaki Kiyomi
Department Of Biochemistry And Cell Biology Institute Of Development And Aging Sciences Graduate Sch
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SOMA RIKA
Institute of Health and Sport Sciences, University of Tsukuba
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KOMATSUZAKI YASUKO
Hatsuishi Hospital
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Mizusawa Hidehiro
Department Of Neurology Tokyo Medical And Dental University
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Mizusawa Hidehiro
Department Of Neurology And Neurological Science (chairman: Prof. Hidehiro Mizusawa) Graduate School
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Soma Rika
Institute Of Health And Sport Sciences University Of Tsukuba:center For Tsukuba Advanced Research Al
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Hayashi Junichi
Institute Of Biological Sciences University Of Tsukuba:center For Tsukuba Advanced Research Alliance
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Hayashi Junichi
Institute Of Biological Scences University Of Tsukuba
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