首页> 外文期刊>The Journal of Nutritional Biochemistry >L-Arginine stimulates the mTOR signaling pathway and protein synthesis in porcine trophectoderm cells.
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L-Arginine stimulates the mTOR signaling pathway and protein synthesis in porcine trophectoderm cells.

机译:L-精氨酸刺激猪滋养外胚层细胞中的mTOR信号通路和蛋白质合成。

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摘要

Impairment of placental growth is a major factor contributing to intrauterine growth retardation (IUGR) in both human pregnancy and animal production. Results of recent studies indicate that administration of L-arginine (Arg) to gestating pigs or sheep with IUGR fetuses can enhance fetal growth. However, the underlying mechanisms are largely unknown. The present study tested the hypothesis that Arg stimulates the mammalian target of rapamycin (mTOR) signaling pathway and protein synthesis in porcine conceptus trophectoderm (pTr2) cells. The cells were cultured for 4 days in Arg-free Dulbecco's modified Eagle's Ham medium containing 10, 50, 100, 200, 350 or 500 muM Arg. Cell numbers, protein synthesis and degradation, as well as total and phosphorylated levels of mTOR, ribosomal protein S6 kinase 1 (p70S6K) and eukaryotic initiation factor 4E-binding protein-1 (4EBP1), were determined. The pTr2 cells exhibited time (0-6 days)- and Arg concentration (10-350 muM)-dependent increases in proliferation. Addition of 100 and 350 muM Arg to culture medium dose-dependently increased (a) protein synthesis and decreased protein degradation and (b) the abundance of total and phosphorylated mTOR, p70S6K and 4EBP1 proteins. Effects of 350 muM Arg on intracellular protein turnover were only modestly affected when nitric oxide synthesis was inhibited. Collectively, these results indicate a novel and important role for Arg in promoting growth of porcine placental cells largely via a nitric-oxide-independent pathway. Additionally, these findings help to explain beneficial effects of Arg supplementation on improving survival and growth of embryos/fetuses in mammals
机译:胎盘生长障碍是导致人类妊娠和动物生产中宫内发育迟缓(IUGR)的主要因素。最近的研究结果表明,向具有IUGR胎儿的妊娠猪或绵羊施用L-精氨酸(Arg)可以促进胎儿生长。但是,基本机制尚不清楚。本研究测试了这样的假设,即精氨酸刺激了猪概念性滋养外胚层(pTr2)细胞中雷帕霉素(mTOR)信号传导途径和蛋白质合成的哺乳动物靶标。将细胞在含有10、50、100、200、350或500μMArg的无Arg的Dulbecco改良Eagle's Ham培养基中培养4天。测定细胞数量,蛋白质合成和降解,以及mTOR,核糖体蛋白S6激酶1(p70S6K)和真核起始因子4E结合蛋白1(4EBP1)的总水平和磷酸化水平。 pTr2细胞显示出时间(0-6天)和Arg浓度(10-350μM)依赖的增殖增加。向培养基中添加100和350μMArg剂量依赖性地增加(a)蛋白质合成和减少的蛋白质降解,以及(b)总的和磷酸化的mTOR,p70S6K和4EBP1蛋白。当抑制一氧化氮合成时,仅适度影响350μMArg对细胞内蛋白质更新的影响。总的来说,这些结果表明Arg主要通过一氧化氮非依赖性途径在促进猪胎盘细胞生长中具有新颖而重要的作用。此外,这些发现有助于解释补充精氨酸对改善哺乳动物胚胎/胎儿存活和生长的有益作用。

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