論文 - 詳細
| RRC ID | 28858 |
|---|---|
| 著者 | Na HJ, Park JS, Pyo JH, Lee SH, Jeon HJ, Kim YS, Yoo MA. |
| タイトル | Mechanism of metformin: inhibition of DNA damage and proliferative activity in Drosophila midgut stem cell. |
| ジャーナル | Mech Ageing Dev |
| Abstract |
Age-related changes in stem cells could have a profound impact on tissue aging and the development of age-related diseases such as cancer. However, the effects of metformin, a recently recognized anti-cancer drug, on stem cell aging remain largely unknown. In the present study, an experiment was set up to investigate the underlying mechanism of metformin's beneficial effects on age-related changes in intestinal stem cells (ISCs) derived from Drosophila midgut. Results showed that metformin reduced age- and oxidative stress-related accumulation of DNA damage marked by Drosophila γH2AX foci and 8-oxo-dG in ISCs and progenitor cells. Metformin also inhibited age and- oxidative stress-related ISC hyperproliferation as well as intestinal hyperplasia. Our study further revealed that the inhibitory effects of metformin on DNA damage accumulation may be due to the down-regulation of age-related and oxidative stress-induced AKT activity. These data indicate that metformin has beneficial effects on age-related changes in ISCs derived from Drosophila midgut. Further, our results suggest a possible impact of DNA damage on stem cell genomic instability, which leads to the development of age-related diseases. Additionally, our study suggests that Drosophila midgut stem cells can be a suitable model system for studying stem cell biology and stem cell aging. |
| 巻・号 | 134(9) |
| ページ | 381-90 |
| 公開日 | 2013-9-1 |
| DOI | 10.1016/j.mad.2013.07.003 |
| PII | S0047-6374(13)00085-7 |
| PMID | 23891756 |
| MeSH | Aging* Animals Animals, Genetically Modified Bromodeoxyuridine / chemistry Cell Proliferation Cellular Senescence DNA Damage / drug effects Drosophila / metabolism Drosophila / physiology* Female Green Fluorescent Proteins / metabolism Hypoglycemic Agents / chemistry Intestines / cytology* Male Metformin / chemistry* Oxidative Stress Proto-Oncogene Proteins c-akt / antagonists & inhibitors Proto-Oncogene Proteins c-akt / metabolism Signal Transduction Stem Cells / cytology* Stem Cells / drug effects* Temperature |
| IF | 4.304 |
| 引用数 | 34 |
| WOS 分野 | GERIATRICS & GERONTOLOGY CELL BIOLOGY |
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 2 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
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