Rapamycin increases oxidative stress response gene expression in adult stem cells.
Rapamycin increases oxidative stress response gene expression in adult stem cells.
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DOI：
10.18632/aging.100451
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发表时间：
2012-04
期刊：
影响因子：
--
通讯作者：
Payne CJ
中科院分区：
文献类型：
--
作者：
Kofman AE;McGraw MR;Payne CJ
平衡静止与增殖对于成体干细胞至关重要，以避免过度增殖和细胞耗竭。在一些模型中，雷帕霉素药物可以逆转干细胞的耗竭，该药物被证明可以在体外抑制细胞衰老并延长动物的寿命。我们假设雷帕霉素会增加成体干细胞中氧化应激反应基因的表达，并且这些基因活性随着年龄的增长而减弱。为了验证我们的假设，我们将小鼠暴露于雷帕霉素，然后检查其精原干细胞（SSC）的转录组。基因表达微阵列分析显示，许多氧化应激反应基因在雷帕霉素处理后上调，包括超氧化物歧化酶1、谷胱甘肽还原酶和δ-氨基乙酰丙酸脱水酶。当我们检查这些基因在 55 周龄野生型 SSC 中的表达时，与 3 周龄 SSC 相比，它们的水平显着降低，表明它们的下调与成体干细胞的衰老过程一致。我们得出的结论是，雷帕霉素诱导的氧化应激反应基因刺激可能会促进SSCs的细胞寿命，而衰老干细胞中基因表达的下降可能反映出SSCs缓解氧化应激（衰老的标志）的潜力减弱。
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.
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影响因子：
64.5
作者：
Hobbs RM;Seandel M;Falciatori I;Rafii S;Pandolfi PP
通讯作者：
Pandolfi PP
DOI：
10.18632/aging.100040
发表时间：
2009-04-20
期刊：
Aging
影响因子：
--
作者：
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通讯作者：
Hall MN
影响因子：
7.8
作者：
Hansen, Malene;Taubert, Stefan;Kenyon, Cynthia
通讯作者：
Kenyon, Cynthia
影响因子：
9.2
作者：
Kapahi, P;Zid, BM;Benzer, S
通讯作者：
Benzer, S
影响因子：
7.8
作者：
Bailey, KJ;Maslov, AY;Pruitt, SC
通讯作者：
Pruitt, SC