Cu-Pyruvaldehyde-bis(N4-methylthiosemicarbazone) (Cu-PTSM), a Metal Complex with Selective NADH-Dependent Reduction by Complex I in Brain Mitochondria: A Potential Radiopharmaceutical for Mitochondria-Functional Imaging with Positron Emission Tomography (PET).
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The reductive retention mechanism of copper (II)-pyruvaldehyde-bis (N4-methylthiosemicarbazone) (Cu-PTSM), a generator-produced positron-emitting 62Cu-labeled radiopharmaceutical, was studied with non-radioactive and radioactive copper. Changes in the chemical form of Cu-PTSM were detected by electron spin resonance spectrometry (ESR) with cold copper. The effects of electron transport chain inhibitors on the reduction of Cu-PTSM were also examined. Rotenone and antimycin A activated the reduction of Cu-PTSM in the brain mitochondria by 1.6-and 1.4-fold, respectively, compared with untreated controls, while thenoyltrifluoroacetone (TTFA) had no effect on the reduction. These results were confirmed with radioactive copper. Furthermore, this reduction of Cu-PTSM was dependent on the protein concentration of mouse brain submitochondrial particle (SMP) with 1mM NADH (0 mg-protein/ml : 1.8±2.5%, 8mg-protein/ml : 69.0±5.5%, each value was % of reduced Cu). Similarly, this reduction depended on NADH concentration at a fixed concentration of SMP (8mg-protein/ml). These results indicated that the electron transport chain, especially complex I, participated in the reduction of Cu-PTSM in brain mitochondria, and this suggested that Cu-PTSM has the potential to act as a functional imaging agent for diagnosis of the electron transport chain.
収録刊行物
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- Biological & Pharmaceutical Bulletin
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Biological & Pharmaceutical Bulletin 18 (8), 1126-1129, 1995
公益社団法人 日本薬学会
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詳細情報 詳細情報について
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- CRID
- 1390282679599071232
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- NII論文ID
- 110003641001
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- NII書誌ID
- AA10885497
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- ISSN
- 13475215
- 09186158
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- PubMed
- 8535408
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- Crossref
- PubMed
- CiNii Articles
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- 使用不可