Rapamycin increases oxidative stress response gene expression in adult stem cells
| Autor: | Christopher J. Payne, Amber E. Kofman, Margeaux R. McGraw |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Male
Aging antioxidant Glutathione reductase Gene Expression Biology testis medicine.disease_cause adult stem cells Transcriptome 03 medical and health sciences Mice 0302 clinical medicine Downregulation and upregulation Gene expression medicine Animals Cells Cultured Cellular Senescence 030304 developmental biology Oligonucleotide Array Sequence Analysis Sirolimus 0303 health sciences Reverse Transcriptase Polymerase Chain Reaction rapamycin Stem Cells TOR Serine-Threonine Kinases Cell Biology Molecular biology Spermatogonia Cell biology Oxidative Stress Stem cell Cell aging 030217 neurology & neurosurgery Oxidative stress Adult stem cell Research Paper |
| Zdroj: | Aging (Albany NY) |
| ISSN: | 1945-4589 |
| Popis: | Balancing quiescence with proliferation is of paramount importance for adult stem cells in order to avoid hyperproliferation and cell depletion. In some models, stem cell exhaustion may be reversed with the drug rapamycin, which was shown can suppress cellular senescence in vitro and extend lifespan in animals. We hypothesized that rapamycin increases the expression of oxidative stress response genes in adult stem cells, and that these gene activities diminish with age. To test our hypothesis, we exposed mice to rapamycin and then examined the transcriptome of their spermatogonial stem cells (SSCs). Gene expression microarray analysis revealed that numerous oxidative stress response genes were upregulated upon rapamycin treatment, including superoxide dismutase 1, glutathione reductase, and delta-aminolevulinate dehydratase. When we examined the expression of these genes in 55-week-old wild type SSCs, their levels were significantly reduced compared to 3-week-old SSCs, suggesting that their downregulation is coincident with the aging process in adult stem cells. We conclude that rapamycin-induced stimulation of oxidative stress response genes may promote cellular longevity in SSCs, while a decline in gene expression in aged stem cells could reflect the SSCs' diminished potential to alleviate oxidative stress, a hallmark of aging. |
| Databáze: | OpenAIRE |
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