Rapamycin induces pluripotent genes associated with avoidance of replicative senescence
| Autor: | Tatyana V. Pospelova, Svetlana G. Zubova, Natalia M Yartzeva, Bykova Tv, Natalia V Katolikova, Valery A. Pospelov |
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| Rok vydání: | 2013 |
| Předmět: |
Homeobox protein NANOG
Senescence Telomerase Cell cycle checkpoint Karyotype Cell Culture Techniques Biology Downregulation and upregulation Report Autophagy Animals Molecular Biology PI3K/AKT/mTOR pathway Cells Cultured Cellular Senescence Cell Proliferation Homeodomain Proteins Sirolimus SOXB1 Transcription Factors Cell Cycle Cell Biology Nanog Homeobox Protein Fibroblasts Embryonic stem cell Cell biology Telomere Rats Octamer Transcription Factor-3 Developmental Biology |
| Zdroj: | Cell cycle (Georgetown, Tex.). 12(24) |
| ISSN: | 1551-4005 |
| Popis: | Primary rodent cells undergo replicative senescence, independent from telomere shortening. We have recently shown that treatment with rapamycin during passages 3–7 suppressed replicative senescence in rat embryonic fibroblasts (REFs), which otherwise occurred by 10–14 passages. Here, we further investigated rapamycin-primed cells for an extended number of passages. Rapamycin-primed cells continued to proliferate without accumulation of senescent markers. Importantly, these cells retained the ability to undergo serum starvation- and etoposide-induced cell cycle arrest. The p53/p21 pathway was functional. This indicates that rapamycin did not cause either transformation or loss of cell cycle checkpoints. We found that rapamycin activated transcription of pluripotent genes, oct-4, sox-2, nanog, as well as further upregulated telomerase (tert) gene. The rapamycin-derived cells have mostly non-rearranged, near-normal karyotype. Still, when cultivated for a higher number of passages, these cells acquired a chromosomal marker within the chromosome 3. We conclude that suppression mTORC1 activity may prevent replicative senescence without transformation of rodent cells. |
| Databáze: | OpenAIRE |
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