| Item type |
文献 / Documents(1) |
| 公開日 |
2020-11-26 |
| アクセス権 |
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アクセス権 |
open access |
| 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 |
| 出版社版DOI |
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|
識別子タイプ |
DOI |
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|
関連識別子 |
https://doi.org/10.1186/s13046-016-0322-2 |
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言語 |
ja |
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|
関連名称 |
10.1186/s13046-016-0322-2 |
| 出版タイプ |
|
|
出版タイプ |
VoR |
|
出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| タイトル |
|
|
タイトル |
Modulation of anti-cancer drug sensitivity through the regulation of mitochondrial activity by adenylate kinase 4 |
|
言語 |
en |
| 著者 |
フジサワ, コウイチ
テライ, シュウジ
タカミ, タロウ
ヤマモト, ナオキ
ヤマサキ, タカヒロ
マツモト, トシヒコ
ヤマグチ, カズヒト
オオワダ, ユウジ
ニシナ, ヒロシ
野間, 隆文
サカイダ, イサオ
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| 抄録 |
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内容記述タイプ |
Abstract |
|
内容記述 |
Background: Adenylate kinase is a key enzyme in the high-energy phosphoryl transfer reaction in living cells. An isoform of this enzyme, adenylate kinase 4 (AK4), is localized in the mitochondrial matrix and is believed to be involved in stress, drug resistance, malignant transformation in cancer, and ATP regulation. However, the molecular basis for the AK4 functions remained to be determined.
Methods: HeLa cells were transiently transfected with an AK4 small interfering RNA (siRNA), an AK4 short hairpin RNA (shRNA) plasmid, a control shRNA plasmid, an AK4 expression vector, and a control expression vector to examine the effect of the AK4 expression on cell proliferation, sensitivity to anti-cancer drug, metabolome, gene expression, and mitochondrial activity.
Results: AK4 knockdown cells treated with short hairpin RNA increased ATP production and showed greater sensitivity to hypoxia and anti-cancer drug, cis-diamminedichloro-platinum (II) (CDDP). Subcutaneous grafting AK4 knockdown cells into nude mice revealed that the grafted cells exhibited both slower proliferation and reduced the tumor sizes in response to CDDP. AK4 knockdown cell showed a increased oxygen consumption rate with FCCP treatment, while AK4 overexpression lowered it. Metabolome analysis showed the increased levels of the tricarboxylic acid cycle intermediates, fumarate and malate in AK4 knockdown cells, while AK4 overexpression lowered them. Electron microscopy detected the increased mitochondrial numbers in AK4 knockdown cells. Microarray analysis detected the increased gene expression of two key enzymes in TCA cycle, succinate dehydrogenase A (SDHA) and oxoglutarate dehydrogenease L (OGDHL), which are components of SDH complex and OGDH complex, supporting the metabolomic results.
Conclusions: We found that AK4 was involved in hypoxia tolerance, resistance to anti-tumor drug, and the regulation of mitochondrial activity. These findings provide a new potential target for efficient anticancer therapies by controlling AK4 expression. |
|
言語 |
en |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
Adenylate kinase |
| キーワード |
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|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
Drug resistance |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
Energy metabolism |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
Flux analysis |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
Hypoxia |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
Metabolome |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
Mitochondria |
| 書誌情報 |
en : Journal of Experimental & Clinical Cancer Research
巻 35,
p. 48,
発行日 2016-03-16
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| 収録物ID |
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|
収録物識別子タイプ |
ISSN |
|
収録物識別子 |
17569966 |
| 出版者 |
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出版者 |
Springer Nature |
|
言語 |
en |
| 出版者 |
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|
出版者 |
BioMed Central |
|
言語 |
en |
| 権利情報 |
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|
言語 |
en |
|
権利情報 |
© 2016 Fujisawa et al. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
| EID |
|
|
識別子 |
310071 |
|
識別子タイプ |
URI |
| 言語 |
|
|
言語 |
eng |
jeccr_35_48.pdf (2.64 MB)
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