title: L-Arginine stimulates the mTOR signaling pathway and protein synthesis in porcine trophectoderm cells.
abstract: 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 μM 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 μM)-dependent increases in proliferation. Addition of 100 and 350 μM 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 μM 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.
authors.affiliation: Research Center for Healthy Breeding of Livestock and Poultry and Key Laboratory for Agro-ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, The Chinese Academy of Sciences, 410125 Hunan, China.
authors.forename: Xiangfeng
authors.initials: X
authors.lastname: Kong
authors.forename: Bie
authors.initials: B
authors.lastname: Tan
authors.forename: Yulong
authors.initials: Y
authors.lastname: Yin
authors.forename: Haijun
authors.initials: H
authors.lastname: Gao
authors.forename: Xilong
authors.initials: X
authors.lastname: Li
authors.forename: Laurie A
authors.initials: LA
authors.lastname: Jaeger
authors.forename: Fuller W
authors.initials: FW
authors.lastname: Bazer
authors.forename: Guoyao
authors.initials: G
authors.lastname: Wu
mesh_terms: D000818:Animals; D001120:Arginine / Q000378:metabolism*; D001755:Blastocyst / Q000166:cytology / Q000187:drug effects; D049109:Cell Proliferation; D002478:Cells, Cultured; D004475:Ectoderm / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D010766:Phosphorylation; D011247:Pregnancy; D014176:Protein Biosynthesis / Q000187:drug effects; D011499:Protein Processing, Post-Translational; D055550:Protein Stability / Q000187:drug effects; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D015398:Signal Transduction; D034421:Sus scrofa; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D014327:Trophoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; C448901:ribosomal protein S6 kinase, 70kD, polypeptide 1