| Item type |
学術雑誌論文 / Journal Article_02(1) |
| 公開日 |
2017-07-19 |
| タイトル |
|
|
タイトル |
Iron-induced epigenetic abnormalities of mouse bone marrow through aberrant activation of aconitase and isocitrate dehydrogenase |
| 言語 |
|
|
言語 |
eng |
| キーワード |
|
|
主題Scheme |
Other |
|
キーワード |
DNA methylation |
| キーワード |
|
|
主題Scheme |
Other |
|
キーワード |
Iron overload |
| キーワード |
|
|
主題Scheme |
Other |
|
キーワード |
Leukemia |
| キーワード |
|
|
主題Scheme |
Other |
|
キーワード |
Myelodysplastic syndrome |
| 資源タイプ |
|
|
資源タイプ |
journal article |
| 著者 |
山本, 昌代
田中, 宏樹
土岐, 康通
畑山, 真弓
伊藤, 巧
Addo, Lynda
進藤, 基博
佐々木, 勝則
生田, 克哉
大竹, 孝明
藤谷, 幹浩
鳥本, 悦宏
高後, 裕
|
| 著者 ローマ字 |
|
|
|
Yamamoto, Masayo |
| 著者 ローマ字 |
|
|
|
Tanaka, Hiroki |
| 著者 ローマ字 |
|
|
|
Toki, Yasumichi |
| 著者 ローマ字 |
|
|
|
Hatayama, Mayumi |
| 著者 ローマ字 |
|
|
|
Ito, Satoshi |
| 著者 ローマ字 |
|
| 著者 ローマ字 |
|
|
|
Shindo, Motohiro |
| 著者 ローマ字 |
|
|
|
Sasaki, Katsunori |
| 著者 ローマ字 |
|
|
|
Ikuta, Katsuya |
| 著者 ローマ字 |
|
|
|
Ohtake, Takaaki |
| 著者 ローマ字 |
|
|
|
Fujiya, Mikihiro |
| 著者 ローマ字 |
|
|
|
Torimoto, Yoshihiro |
| 著者 ローマ字 |
|
|
|
Kohgo, Yutaka |
| 書誌情報 |
International Journal of Hematology
巻 104,
号 4,
p. 491-501,
発行日 2016-10-01
|
| ISSN |
|
|
収録物識別子タイプ |
ISSN |
|
収録物識別子 |
0925-5710 |
| DOI |
|
|
関連タイプ |
isVersionOf |
|
|
識別子タイプ |
DOI |
|
|
関連識別子 |
10.1007/s12185-016-2054-7 |
| 識別番号 その他 |
|
|
内容記述タイプ |
Other |
|
内容記述 |
PMID：27380194 |
| 抄録 |
|
|
内容記述タイプ |
Abstract |
|
内容記述 |
Iron overload remains a concern in myelodysplastic syndrome (MDS) patients. Iron chelation therapy (ICT) thus plays an integral role in the management of these patients. Moreover, ICT has been shown to prolong leukemia-free survival in MDS patients; however, the mechanisms responsible for this effect are unclear. Iron is a key molecule for regulating cytosolic aconitase 1 (ACO1). Additionally, the mutation of isocitrate dehydrogenase (IDH), the enzyme downstream of ACO1 in the TCA cycle, is associated with epigenetic abnormalities secondary to 2-hydroxyglutarate (2-HG) and DNA methylation. However, epigenetic abnormalities observed in many MDS patients occur without IDH mutation. We hypothesized that iron itself activates the ACO1-IDH pathway, which may increase 2-HG and DNA methylation, and eventually contribute to leukemogenesis without IDH mutation. Using whole RNA sequencing of bone marrow cells in iron-overloaded mice, we observed that the enzymes, phosphoglucomutase 1, glycogen debranching enzyme, and isocitrate dehydrogenase 1 (Idh1), which are involved in glycogen and glucose metabolism, were increased. Digital PCR further showed that Idh1 and Aco1, enzymes involved in the TCA cycle, were also elevated. Additionally, enzymatic activities of TCA cycle and methylated DNA were increased. Iron chelation reversed these phenomena. In conclusion, iron activation of glucose metabolism causes an increase of 2-HG and DNA methylation. |
| 注記 |
|
|
内容記述タイプ |
Other |
|
注記 |
The final publication is available at Springer via http://dx.doi.org/10.1007/s12185-016-2054-7 |
| 資源タイプ |
|
|
内容記述タイプ |
Other |
|
資源タイプ |
text |
| 著者版フラグ |
|
|
出版タイプ |
AM |
| フォーマット |
|
|
内容記述タイプ |
Other |
|
内容記述 |
application/pdf |
| ID(XooNIps) |
|
|
|
27380194 |
| 閲覧数(XooNIps) |
|
| ダウンロード数(XooNIps) |
|
|
|
396 |
6755.pdf (12.9 MB)
