肠道干细胞和祖细胞中Tor/Myc信号轴的激活会影响果蝇的寿命、抗逆性和新陈代谢。

Activation of the Tor/Myc signaling axis in intestinal stem and progenitor cells affects longevity, stress resistance and metabolism in drosophila.

作者信息

Strilbytska Olha M, Semaniuk Uliana V, Storey Kenneth B, Edgar Bruce A, Lushchak Oleh V

机构信息

Department of Biochemistry and Biotechnology, Vasyl Stefanyk Precarpathian National University, 57 Shevchenka str., Ivano-Frankivsk 76018, Ukraine.

Institute of Biochemistry, Carleton University, 1125 Colonel By Drive, Ottawa, Ontario, K1S 5B6, Canada.

出版信息

Comp Biochem Physiol B Biochem Mol Biol. 2017 Jan;203:92-99. doi: 10.1016/j.cbpb.2016.09.008. Epub 2016 Sep 29.

Abstract

The TOR (target of rapamycin) signaling pathway and the transcriptional factor Myc play important roles in growth control. Myc acts, in part, as a downstream target of TOR to regulate the activity and functioning of stem cells. Here we explore the role of TOR-Myc axis in stem and progenitor cells in the regulation of lifespan, stress resistance and metabolism in Drosophila. We found that both overexpression of rheb and myc-rheb in midgut stem and progenitor cells decreased the lifespan and starvation resistance of flies. TOR activation caused higher survival under malnutrition conditions. Furthermore, we demonstrate gut-specific activation of JAK/STAT and insulin signaling pathways to control gut integrity. Both genetic manipulations had an impact on carbohydrate metabolism and transcriptional levels of metabolic genes. Our findings indicate that activation of the TOR-Myc axis in midgut stem and progenitor cells influences a variety of traits in Drosophila.

摘要

雷帕霉素靶蛋白(TOR)信号通路和转录因子Myc在生长控制中发挥着重要作用。Myc部分作为TOR的下游靶点,调节干细胞的活性和功能。在此,我们探究TOR-Myc轴在果蝇干细胞和祖细胞中对寿命、抗逆性及新陈代谢调节的作用。我们发现,在中肠干细胞和祖细胞中过表达rheb和myc-rheb均会缩短果蝇寿命并降低其饥饿抗性。TOR激活使果蝇在营养不良条件下具有更高的存活率。此外,我们证明肠道特异性激活JAK/STAT和胰岛素信号通路可控制肠道完整性。这两种基因操作均对碳水化合物代谢及代谢基因的转录水平产生影响。我们的研究结果表明,中肠干细胞和祖细胞中TOR-Myc轴的激活会影响果蝇的多种性状。

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