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Radiolabeled Cu-ATSM as a novel indicator of overreduced intracellular state due to mitochondrial dysfunction: studies with mitochondrial DNA-less p0 cells and cybrids carrying MELAS mitochondrial DNA mutation
https://repo.qst.go.jp/records/46258
https://repo.qst.go.jp/records/46258676312d6-623e-454c-8875-a991d551169f
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
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| 公開日 | 2012-02-01 | |||||
| タイトル | ||||||
| タイトル | Radiolabeled Cu-ATSM as a novel indicator of overreduced intracellular state due to mitochondrial dysfunction: studies with mitochondrial DNA-less p0 cells and cybrids carrying MELAS mitochondrial DNA mutation | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
| 資源タイプ | journal article | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 著者 |
Yoshii, Yukie
× Yoshii, Yukie× Yoneda, Makoto× Ikawa, Masamichi× Furukawa, Takako× Kiyono, Yasushi× Mori, Tetsuya× Yoshii, Hiroshi× Oyama, Nobuyuki× Okazawa, Hidehiko× Saga, Tsuneo× Fujibayashi, Yasuhisa× 吉井 幸恵× 古川 高子× 清野 泰× 吉井 裕× 佐賀 恒夫× 藤林 康久 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Objectives Radiolabeled Cu-diacetyl-bis (N4-methylthiosemicarbazone) ('Cu-ATSM), including 60/62/64Cu-ATSM, is a potential imaging agent of hypoxic tumors for positron emission tomography (PET). We have reported that 'Cu-ATSM is trapped in tumor cells under intracellular overreduced states, e.g., hypoxia. Here we evaluated 'Cu-ATSM as an indicator of intracellular overreduced states in mitochondrial disorders using cell lines with mitochondrial dysfunction. \nMethods Mitochondrial DNA-less p0206 cells; the parental 143B human osteosarcoma cells; the cybrids carrying mutated mitochondria from a patient of mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) (2SD); and that carrying wild-type one (2SA) were used. Cells were treated under normoxia or hypoxia, and 64Cu-ATSM uptake was examined to compare it with levels of biological reductant NADH and NADPH. \nResults p0206 cells showed higher 64Cu-ATSM uptake than control 143B cells under normoxia, whereas 64Cu-ATSM uptake was not significantly increased under hypoxia in p0206 cells. Additionally, 64Cu-ATSM uptake showed correlate change to the NADH and NADPH levels, but not oxygenic conditions. 2SD cells showed increased 64Cu-ATSM uptake under normoxia as compared with the control 2SA, and 64Cu-ATSM uptake followed NADH and NADPH levels, but not oxygenic conditions. \nConclusions 64Cu-ATSM accumulated in cells with overreduced states due to mitochondrial dysfunction, even under normoxia. We recently reported that 62Cu-ATSM-PET can visualize stroke-like episodes maintaining oxygen supply in MELAS patients. Taken together, our data indicate that 'Cu-ATSM uptake reflects overreduced intracellular states, despite oxygenic conditions; thus, 'Cu-ATSM would be a promising marker of intracellular overreduced states for disorders with mitochondrial dysfunction, such as MELAS, Parkinson's disease and Alzheimer's disease. \nAbbreviations: Cu-ATSM, Cu-diacetyl-bis (N4-methylthiosemicarbazone); MELAS, mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes; mtDNA, mitochondrial DNA; PET, positron emission tomography |
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| 書誌情報 |
Nuclear Medicine and Biology 巻 39, 号 12, p. 177-185, 発行日 2011-10 |
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| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 0969-8051 | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.1016/j.nucmedbio.2011.08.008 | |||||
