1992 Fiscal Year Final Research Report Summary
Studies on Pathogenesis of Mitochondrial Diseases
| Project/Area Number |
02304043
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| Research Category |
Grant-in-Aid for Co-operative Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
Pediatrics
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| Research Institution | TOHOKU UNIVERSITY |
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Principal Investigator |
TADA Keiya TOHOKU UNIVERSITY SCHOOL OF MEDICINE, DEPARTMENT OF PEDIATRICS, PROFESSOR, 医学部, 教授 (20046907)
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| Co-Investigator(Kenkyū-buntansha) |
MIYABAHASHI Shigeaki TOHOKU UNIVERSITY,SCHOOL OF MEDICINE,ASSISTANT PROFESSOR, 医学部, 講師 (20174203)
宝来 聰 国立遺伝学研究所, 助教授 (40126157)
WADA Yoshiroh NAGOYA CITY UNIVERSITY MEDICAL SCHOOL,DEPARTMENT OF PEDIATRICS,PROFESSOR, 医学部, 教授 (30004849)
OZAWA Takayuki NAGOYA UNIVERSITY SCHOOL OF MEDICINE, DEPARTMENT OF BIOCHEMISTRY, PROFESSOR, 医学部, 教授 (80022771)
KAGAWA Yasuo JICHI MEDICAL SCHOOL, DEPARTMENT OF BIOCHEMISTRY, PROFESSOR, 教授 (30048962)
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| Project Period (FY) |
1990 – 1992
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| Keywords | mitochondrial encephalomyopathy / mitochondrial DNA / MELAS / heteroplasmy / oxidative phosphorylation / fibroblasts / SV40 cell line / p0 cells |
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| Research Abstract |
We investigated the distribution and expression of 3243 mutation,the most common genetic defect, in the skeletal muscle of 18 patients with MELAS. This mtDNA mutation was present in 12 of 18 patients(67%). The proportion of this mutation in muscle ranged from 50 to 80% and was significantly higher in the patients with MELAS than in their oligosymptomatic or asymptomatic relatives on family study. Furthermore the proportion of 3243 mutation in skeletal muscle had good relation to an age of suffering first stroke like attack.
In the enzymatic study,complex I-III activity was markedly decreased in the skeletal muscle mitochondria of all the patients with this mutation. The decrease of complex I had also clear relation to the population of this mtDNA mutation. It is reason that complex I is more components of peptides encoding from mtDNA than complex IV(COX), and mtDNA mutation is more harmful to its assembly.This fact is likely to accord a common decrease of complex I activity in muscle mitochondria from MELAS patients.
We investigated the cybrid colons by fusing p0-HeLa cell and nuclear DNA- less fibroblasts with 3243 mutation showed quickly declined activity of COX at consisting more than 95% of this mutation. However the activity of complex I already decreased at lower population of this mutation instead of the normal activity of COX.
Our data seems to indicate that 3243 mutation directly affects the inhibit of oxidative phospholyration and its quantity is a main factor to onset of MELAS with this mutation.
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[Publications] Haginoya, K., Miyabayashi, S., Iinuma, K., Okino, E., Maesaka, H. & Tada, K.: "Cytochrome C oxidase-deficient mitochondria in mitochondrial myopathy." Pediatr.Neurol.8(1). 13-18 (1992)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Miyabayashi, S., Endo, H., Haginoya, K., Su, C.C., Watanabe, T., Irimada, K., Tsuchida, S. & Tada, K.: "Familial MELAS(mitochondrial myopathy,encephalopathy,lactic acidosis,and stroke-like episodes)with cytochrome b deficiency."
Description
「研究成果報告書概要(欧文)」より
