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Mitochondrial complex III in larval stage of Echinococcus multilocularis as a potential chemotherapeutic target and in vivo efficacy of atovaquone against primary hydatid cysts
http://hdl.handle.net/10069/39549
http://hdl.handle.net/10069/39549a7a88e02-2022-4eae-8140-2f9a06f8071c
名前 / ファイル | ライセンス | アクション |
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ParInt75_102004.pdf (1.8 MB)
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Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2019-11-20 | |||||
タイトル | ||||||
タイトル | Mitochondrial complex III in larval stage of Echinococcus multilocularis as a potential chemotherapeutic target and in vivo efficacy of atovaquone against primary hydatid cysts | |||||
言語 | ||||||
言語 | eng | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Echinococcus multilocularis | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Oxidative phosphorylation | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Fumarate respiration | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Mitochondrial complex III | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Atovaquone | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Drug target | |||||
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 | |||||
著者 |
Enkai, Shigehiro
× Enkai, Shigehiro× Inaoka, Daniel Ken× Kouguchi, Hirokazu× Irie, Takao× Yagi, Kinpei× Kita, Kiyoshi |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Echinococcus multilocularis employs aerobic and anaerobic respiration pathways for its survival in the specialized environment of the host. Under anaerobic conditions, fumarate respiration has been identified as a promising target for drug development against E. multilocularis larvae, although the relevance of oxidative phosphorylation in its survival remains unclear. Here, we focused on the inhibition of mitochondrial cytochrome bc1 complex (complex III) and evaluated aerobic respiratory activity using mitochondrial fractions from E. multilocularis protoscoleces. An enzymatic assay revealed that the mitochondrial fractions possessed NADH-cytochrome c reductase (mitochondrial complexes I and III) and succinate-cytochrome c reductase (mitochondrial complexes II and III) activities in the aerobic pathway. Enzymatic analysis showed that atovaquone, a commercially available anti-malarial drug, inhibited mitochondrial complex III at 1.5 nM (IC50). In addition, culture experiments revealed the ability of atovaquone to kill protoscoleces under aerobic conditions, but not under anaerobic conditions, indicating that protoscoleces altered their respiration system to oxidative phosphorylation or fumarate respiration depending on the oxygen supply. Furthermore, combined administration of atovaquone with atpenin A5, a quinone binding site inhibitor of complex II, completely killed protoscoleces in the culture. Thus, inhibition of both complex II and complex III was essential for strong antiparasitic effect on E. multilocularis. Additionally, we demonstrated that oral administration of atovaquone significantly reduced primary alveolar hydatid cyst development in the mouse liver, compared with the untreated control, indicating that complex III is a promising target for development of anti-echinococcal drug. | |||||
書誌情報 |
Parasitology International 巻 75, p. 102004, 発行日 2019-10-31 |
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出版者 | ||||||
出版者 | Elsevier B.V. | |||||
ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 13835769 | |||||
DOI | ||||||
関連タイプ | isIdenticalTo | |||||
識別子タイプ | DOI | |||||
関連識別子 | 10.1016/j.parint.2019.102004 | |||||
権利 | ||||||
権利情報 | c 2019 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/BY/4.0/). | |||||
著者版フラグ | ||||||
出版タイプ | VoR | |||||
出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
引用 | ||||||
内容記述タイプ | Other | |||||
内容記述 | Parasitology International, 75, art.no.102004; 2020 |