A load of mice to hypergravity causes AMPKα repression with liver injury, which is overcome by preconditioning loads via Nrf2.
A load of mice to hypergravity causes AMPKα repression with liver injury, which is overcome by preconditioning loads via Nrf2.
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DOI：
10.1038/srep15643
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发表时间：
2015-10-23
影响因子：
4.6
通讯作者：
Kim SG
中科院分区：
文献类型：
--
作者：
Lee SG;Lee CG;Wu HM;Oh CS;Chung SW;Kim SG
了解超重力对能量稳态的影响对于管理航天任务的适当生理对策是必要的。这项研究调查了小鼠的单次或多次超重力负荷是否对与能量代谢相关的分子有影响。在肝脏中，+9Gz 超重力负载 1 小时后，AMPKα 水平及其信号传导受到抑制 6 小时，然后逐渐恢复正常。 AMPKα 水平在 3 次负载至 +9 Gz 后恢复，表明预处理适应。在cDNA微阵列分析中，+9 Gz差异表达了221个基因，下调的基因包括Nrf2靶标。 Nrf2基因敲除消除了3次负载至+9 Gz引起的AMPKα的恢复，表明Nrf2在AMPKα的适应性增加中发挥作用。此外，+9 Gz 应激降低了 STAT3、FOXO1/3 和 CREB 水平，且在静息时间内减弱。同样，肝脏中的细胞凋亡标记物增强，表明肝脏可能容易受到超重力应激。预处理负荷可防止肝细胞凋亡。总体而言，小鼠+9Gz超重力负荷会导致AMPKα抑制并导致肝损伤，这可以通过Nrf2介导的多重超重力负荷来克服。
An understanding of the effects of hypergravity on energy homeostasis is necessary in managing proper physiological countermeasures for aerospace missions. This study investigated whether a single or multiple load(s) of mice to hypergravity has an effect on molecules associated with energy metabolism. In the liver, AMPKα level and its signaling were repressed 6 h after a load to +9 Gz hypergravity for 1 h, and then gradually returned toward normal. AMPKα level was restored after 3 loads to +9 Gz, suggestive of preconditioning adaptation. In cDNA microarray analyses, 221 genes were differentially expressed by +9 Gz, and the down-regulated genes included Nrf2 targets. Nrf2 gene knockout abrogated the recovery of AMPKα elicited by 3 loads to +9 Gz, indicating that Nrf2 plays a role in the adaptive increase of AMPKα. In addition, +9 Gz stress decreased STAT3, FOXO1/3 and CREB levels, which was attenuated during the resting time. Similarly, apoptotic markers were enhanced in the liver, indicating that the liver may be vulnerable to hypergravity stress. Preconditioning loads prevented hepatocyte apoptosis. Overall, a load of mice to +9 Gz hypergravity causes AMPKα repression with liver injury, which may be overcome by multiple loads to hypergravity as mediated by Nrf2.