| 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
|
| リソース情報 |
| ショウジョウバエ |
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