Functional integrity of mitochondrial genomes in human platelets and autopsied brain tissues from elderly patients with Alzheimer’s disease

DOI Web Site 被引用文献14件
  • Sayaka Ito
    Institute of Biological Sciences, Institute of Health and Sport Sciences, and Center for Tsukuba Advanced Research Alliance, University of Tsukuba, Ibaraki 305-8572, Japan; Department of Biochemistry and Cell Biology, Institute of Gerontology, Nippon Medical School, Kawasaki, Kanagawa 211-8533, Japan; Women’s University of Nutrition, Sakado, Saitama 350-0288, Japan; Hatsuishi Hospital, Kashiwa, Chiba 277-0885, Japan; and Department of Neurology, Tokyo Medical and Dental University, Tokyo 113-8519,...
  • Shigeo Ohta
    Institute of Biological Sciences, Institute of Health and Sport Sciences, and Center for Tsukuba Advanced Research Alliance, University of Tsukuba, Ibaraki 305-8572, Japan; Department of Biochemistry and Cell Biology, Institute of Gerontology, Nippon Medical School, Kawasaki, Kanagawa 211-8533, Japan; Women’s University of Nutrition, Sakado, Saitama 350-0288, Japan; Hatsuishi Hospital, Kashiwa, Chiba 277-0885, Japan; and Department of Neurology, Tokyo Medical and Dental University, Tokyo 113-8519,...
  • Kiyomi Nishimaki
    Institute of Biological Sciences, Institute of Health and Sport Sciences, and Center for Tsukuba Advanced Research Alliance, University of Tsukuba, Ibaraki 305-8572, Japan; Department of Biochemistry and Cell Biology, Institute of Gerontology, Nippon Medical School, Kawasaki, Kanagawa 211-8533, Japan; Women’s University of Nutrition, Sakado, Saitama 350-0288, Japan; Hatsuishi Hospital, Kashiwa, Chiba 277-0885, Japan; and Department of Neurology, Tokyo Medical and Dental University, Tokyo 113-8519,...
  • Yasuo Kagawa
    Institute of Biological Sciences, Institute of Health and Sport Sciences, and Center for Tsukuba Advanced Research Alliance, University of Tsukuba, Ibaraki 305-8572, Japan; Department of Biochemistry and Cell Biology, Institute of Gerontology, Nippon Medical School, Kawasaki, Kanagawa 211-8533, Japan; Women’s University of Nutrition, Sakado, Saitama 350-0288, Japan; Hatsuishi Hospital, Kashiwa, Chiba 277-0885, Japan; and Department of Neurology, Tokyo Medical and Dental University, Tokyo 113-8519,...
  • Rika Soma
    Institute of Biological Sciences, Institute of Health and Sport Sciences, and Center for Tsukuba Advanced Research Alliance, University of Tsukuba, Ibaraki 305-8572, Japan; Department of Biochemistry and Cell Biology, Institute of Gerontology, Nippon Medical School, Kawasaki, Kanagawa 211-8533, Japan; Women’s University of Nutrition, Sakado, Saitama 350-0288, Japan; Hatsuishi Hospital, Kashiwa, Chiba 277-0885, Japan; and Department of Neurology, Tokyo Medical and Dental University, Tokyo 113-8519,...
  • Shin-ya Kuno
    Institute of Biological Sciences, Institute of Health and Sport Sciences, and Center for Tsukuba Advanced Research Alliance, University of Tsukuba, Ibaraki 305-8572, Japan; Department of Biochemistry and Cell Biology, Institute of Gerontology, Nippon Medical School, Kawasaki, Kanagawa 211-8533, Japan; Women’s University of Nutrition, Sakado, Saitama 350-0288, Japan; Hatsuishi Hospital, Kashiwa, Chiba 277-0885, Japan; and Department of Neurology, Tokyo Medical and Dental University, Tokyo 113-8519,...
  • Yasuko Komatsuzaki
    Institute of Biological Sciences, Institute of Health and Sport Sciences, and Center for Tsukuba Advanced Research Alliance, University of Tsukuba, Ibaraki 305-8572, Japan; Department of Biochemistry and Cell Biology, Institute of Gerontology, Nippon Medical School, Kawasaki, Kanagawa 211-8533, Japan; Women’s University of Nutrition, Sakado, Saitama 350-0288, Japan; Hatsuishi Hospital, Kashiwa, Chiba 277-0885, Japan; and Department of Neurology, Tokyo Medical and Dental University, Tokyo 113-8519,...
  • Hidehiro Mizusawa
    Institute of Biological Sciences, Institute of Health and Sport Sciences, and Center for Tsukuba Advanced Research Alliance, University of Tsukuba, Ibaraki 305-8572, Japan; Department of Biochemistry and Cell Biology, Institute of Gerontology, Nippon Medical School, Kawasaki, Kanagawa 211-8533, Japan; Women’s University of Nutrition, Sakado, Saitama 350-0288, Japan; Hatsuishi Hospital, Kashiwa, Chiba 277-0885, Japan; and Department of Neurology, Tokyo Medical and Dental University, Tokyo 113-8519,...
  • Jun-Ichi Hayashi
    Institute of Biological Sciences, Institute of Health and Sport Sciences, and Center for Tsukuba Advanced Research Alliance, University of Tsukuba, Ibaraki 305-8572, Japan; Department of Biochemistry and Cell Biology, Institute of Gerontology, Nippon Medical School, Kawasaki, Kanagawa 211-8533, Japan; Women’s University of Nutrition, Sakado, Saitama 350-0288, Japan; Hatsuishi Hospital, Kashiwa, Chiba 277-0885, Japan; and Department of Neurology, Tokyo Medical and Dental University, Tokyo 113-8519,...

抄録

<jats:p> 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 <jats:sup>0</jats:sup> ) HeLa cells was carried out by fusion of platelets or synaptosomal fractions of autopsied brain tissues with ρ <jats:sup>0</jats:sup> HeLa cells. The results showed that mtDNA in postmortem brain tissue survives for a long time without degradation and could be rescued in ρ <jats:sup>0</jats:sup> 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. </jats:p>

収録刊行物

被引用文献 (14)*注記

もっと見る

キーワード

詳細情報 詳細情報について

問題の指摘

ページトップへ