Aspartate inhibits LPS-induced MAFbx and MuRF1 expression in skeletal muscle in weaned pigs by regulating Akt, AMPKα and FOXO1
Aspartate inhibits LPS-induced MAFbx and MuRF1 expression in skeletal muscle in weaned pigs by regulating Akt, AMPKα and FOXO1
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DOI：
10.1177/1753425916673443
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发表时间：
2017-01-01
期刊：
影响因子：
3.2
通讯作者：
Hu, Chien-An Andy
中科院分区：
文献类型：
--
作者：
Liu, Yulan;Wang, Xiuying;Hu, Chien-An Andy
感染和炎症会导致肌肉质量和肌原纤维蛋白迅速损失（肌肉萎缩）。此外，天冬氨酸（Asp）是哺乳动物细胞中蛋白质合成所必需的。我们假设 Asp 可以减轻仔猪模型中 LPS 诱导的肌肉萎缩。将24头断奶仔猪分配至4个处理，包括未激发对照、LPS激发对照、LPS+0.5%Asp和LPS+1.0%Asp。第 21 天，对仔猪进行腹腔注射。注射LPS（100 ug/kg BM）或生理盐水。注射后4小时，收集血液、腓肠肌和背最长肌样本进行生化和分子分析。天冬氨酸降低血浆中皮质醇和胰高血糖素的浓度。此外，Asp增加了肌肉中的蛋白质和RNA含量，并降低了肌肉萎缩F-box（MAFbx）和肌肉环指1（MuRF1）的mRNA表达。此外，Asp 降低了 AMPK α 的磷酸化，但增加了肌肉中 Akt 和 Forkhead Box O (FOXO) 1 的磷酸化。我们的结果表明，Asp 通过激活 Akt 信号传导以及抑制 AMPK α 和 FOXO1 信号传导来抑制 LPS 诱导的 MAFbx 和 MuRF1 表达。
Infection and inflammation can result in the rapid loss of muscle mass and myofibrillar proteins (muscle atrophy). In addition, aspartate (Asp) is necessary for protein synthesis in mammalian cells. We hypothesized that Asp could attenuate LPS-induced muscle atrophy in a piglet model. Twenty-four weaning piglets were allotted to four treatments, including non-challenged control, LPS challenged control, LPS+0.5% Asp and LPS+1.0% Asp. On d 21, the piglets were injected with i.p. injection of LPS (100 ug/kg BM) or saline. At 4 h post-injection, blood, gastrocnemius and longissimus dorsi muscles samples were collected for biochemical and molecular analyses. Asp decreased the concentrations of cortisol and glucagon in plasma. In addition, Asp increased protein and RNA contents in muscles, and decreased mRNA expression of muscle atrophy F-box (MAFbx) and muscle RING finger 1 (MuRF1). Moreover, Asp decreased phosphorylation of AMPK alpha but increased phosphorylation of Akt and Forkhead Box O (FOXO) 1 in the muscles. Our results indicate that Asp suppresses LPS-induced MAFbx and MuRF1 expression via activation of Akt signaling, and inhibition of AMPK alpha and FOXO1 signaling.