Mst1-FoxO signaling protects Naïve T lymphocytes from cellular oxidative stress in mice.
Mst1-FoxO signaling protects Naïve T lymphocytes from cellular oxidative stress in mice.
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DOI：
10.1371/journal.pone.0008011
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发表时间：
2009-11-24
期刊：
影响因子：
3.7
通讯作者：
Lim DS
中科院分区：
文献类型：
--
作者：
Choi J;Oh S;Lee D;Oh HJ;Park JY;Lee SB;Lim DS
The Ste-20 family kinase Hippo restricts cell proliferation and promotes apoptosis for proper organ development in Drosophila. In C. elegans, Hippo homolog also regulates longevity. The mammalian Ste20-like protein kinase, Mst1, plays a role in apoptosis induced by various types of apoptotic stress. Mst1 also regulates peripheral naïve T cell trafficking and proliferation in mice. However, its functions in mammals are not fully understood. Here, we report that the Mst1-FoxO signaling pathway plays a crucial role in survival, but not apoptosis, of naïve T cells. In Mst1−/− mice, peripheral T cells showed impaired FoxO1/3 activation and decreased FoxO protein levels. Consistently, the FoxO targets, Sod2 and catalase, were significantly down-regulated in Mst1−/− T cells, thereby resulting in elevated levels of intracellular reactive oxygen species (ROS) and induction of apoptosis. Expression of constitutively active FoxO3a restored Mst1−/− T cell survival. Crossing Mst1 transgenic mice (Mst1 Tg) with Mst1−/− mice reduced ROS levels and restored normal numbers of peripheral naïve T cells in Mst1 Tg;Mst1−/− progeny. Interestingly, peripheral T cells from Mst1−/− mice were hypersensitive to γ-irradiation and paraquat-induced oxidative stresses, whereas those from Mst1 Tg mice were resistant. These data support the hypothesis that tolerance to increased levels of intracellular ROS provided by the Mst1-FoxOs signaling pathway is crucial for the maintenance of naïve T cell homeostasis in the periphery.
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影响因子：
30.5
作者：
通讯作者：
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影响因子：
30.5
作者：
Katagiri, Koko;Imamura, Masashi;Kinashi, Tatsuo
通讯作者：
Kinashi, Tatsuo
影响因子：
64.5
作者：
Harvey, KF;Pfleger, CM;Hariharan, IK
通讯作者：
Hariharan, IK
影响因子：
30.5
作者：
Katagiri, K;Ohnishi, N;Kinashi, T
通讯作者：
Kinashi, T
影响因子：
3.3
作者：
Cemek, Mustafa;Enginar, Huseyin;Unak, Perihan
通讯作者：
Unak, Perihan