| Project/Area Number |
11670144
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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 |
Pathological medical chemistry
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| Research Institution | KYUSHU UNIVERSITY |
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Principal Investigator |
KANG Dongchon Grduate Sch.Med.Sci., KYUSHU UNIVERSITY Assoc.Prof., 大学院・医学研究院, 助教授 (80214716)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1999: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | mitochondrial DNA / MPP+ / Parkinson / DNA replication / Oxidative damage of DNA / hMTH1 / 酸化障害 / DNA修復 |
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| Research Abstract |
Inhibition of mitochondrial DNA replication and resolution of D-loop by MPP+ 1-Methyl-4-phenylpyridinium ion (MPP+) selectively accumulates in substantia nygral cells, thereby causing Parkinsonism. We found that MPP+ selectively inhibits mitochondrial DNA replication but not nuclear DNA replication. The decrease in mitochondrial DNA by the inhibition of mitochondrial DNA replication can be a mechanism by which mitochondrial functions are impaired. MPP+ does not inhibit DNA polymerase γ that is a DNA polymerase responsible for mitochondrial DNA replication. On the other hand MPP+ rapidly depletes nascent strands of mitochondrial DNA in vivo and in oraganello. The decrease in the nascent strands is observed as early as 1 min after the addition of MPP+ in organello, strongly suggesting that MPP+ acts on an early step of mitochondrial DNA replication. We found that MPP+ inhibits the replication by ever unknown mechanism. ie., MPP+ resolves mitochondrial D-loop structure, a mitochondria DNA specific replication intermediate. Furthermore we have found that the resolution is due to the forced change by MPP+ in conformation of a brabched structure contained in the D-loop.
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