Item type |
学術雑誌論文 / Journal Article(1) |
公開日 |
2024-02-20 |
タイトル |
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言語 |
en |
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タイトル |
Fumarate respiration of Fasciola flukes as a potential drug target |
言語 |
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言語 |
eng |
キーワード |
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言語 |
en |
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主題Scheme |
Other |
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主題 |
Fasciola |
キーワード |
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言語 |
en |
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主題Scheme |
Other |
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主題 |
respiratory chain |
キーワード |
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言語 |
en |
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主題Scheme |
Other |
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主題 |
drug target |
キーワード |
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言語 |
en |
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主題Scheme |
Other |
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主題 |
fumarate respiration |
キーワード |
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言語 |
en |
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主題Scheme |
Other |
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主題 |
adult |
キーワード |
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言語 |
en |
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主題Scheme |
Other |
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主題 |
newly excysted juveniles |
資源タイプ |
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資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
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資源タイプ |
journal article |
著者 |
Tashibu, Atsushi
Inaoka, Daniel Ken
Sakamoto, Kimitoshi
Murakami, Kenji
Zannatul, Ferdoush
Kita, Kiyoshi
Ichikawa-Seki, Madoka
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抄録 |
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内容記述タイプ |
Abstract |
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内容記述 |
Fascioliasis is a neglected tropical zoonotic disease caused by liver flukes belonging to the genus Fasciola. The emergence of resistance to triclabendazole, the only World Health Organization-recommended drug for this disease, highlights the need for the development of new drugs. Helminths possess an anaerobic mitochondrial respiratory chain (fumarate respiration) which is considered a potential drug target. This study aimed to evaluate the occurrence of fumarate respiration in Fasciola flukes. We analyzed the properties of the respiratory chain of Fasciola flukes in both adults and newly excysted juveniles (NEJs). Fasciola flukes travel and mature through the stomach, bowel, and abdominal cavity to the liver, where oxygen levels gradually decline. High fumarate reductase activity was observed in the mitochondrial fraction of adult Fasciola flukes. Furthermore, rhodoquinone-10 (RQ10 Em’= −63 mV), a lowpotential electron mediator used in fumarate respiration was found to be predominant in adults. In contrast, the activity of oxygen respiration was low in adults. Rotenone, atpenin A5, and ascochlorin, typical inhibitors of mitochondrial enzymes in complexes I, II, and III, respectively, inhibit the activity of each enzyme in the adult mitochondrial fraction. These inhibitors were then used for in vitro viability tests of NEJs. Under aerobic conditions, NEJs were killed by rotenone or ascochlorin, which inhibit aerobic respiration (complex I–III), whereas atpenin A5, which inhibits complex II involved in fumarate respiration, did not affect NEJs. Moreover, ubiquinone-10 (UQ10 Em’= +110 mV), which is used in oxidative respiration, was detected in NEJs, in addition to RQ10. In contrast, under anaerobic conditions, rotenone and atpenin A5, which inhibit fumarate respiration (complex I–II), were crucial for NEJs. These findings demonstrate that NEJs have active hybrid respiration, in which they can properly use both oxygen and fumarate respiration, depending on oxygen availability. Thus, fumarate respiration is a promising drug target for Fasciola flukes, because it plays an essential role in both adults and NEJs. |
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言語 |
en |
書誌情報 |
en : Frontiers in Cellular and Infection Microbiology
巻 13,
p. art. no. 1302114,
発行日 2024-01-25
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出版者 |
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言語 |
en |
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出版者 |
Frontiers Media SA |
ISSN |
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収録物識別子タイプ |
EISSN |
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収録物識別子 |
2235-2988 |
DOI |
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関連タイプ |
isIdenticalTo |
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識別子タイプ |
DOI |
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関連識別子 |
10.3389/fcimb.2023.1302114 |
権利 |
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言語 |
en |
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権利情報 |
© 2024 Tashibu, Inaoka, Sakamoto, Murakami, Zannatul, Kita and Ichikawa-Seki. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
著者版フラグ |
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出版タイプ |
VoR |
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出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
引用 |
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内容記述タイプ |
Other |
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内容記述 |
Frontiers in Cellular and Infection Microbiology, 13, art. no. 1302114; 2024 |
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言語 |
en |