title: Putrescine stimulates the mTOR signaling pathway and protein synthesis in porcine trophectoderm cells.
abstract: Insufficient placental growth is a major factor contributing to intrauterine growth retardation in mammals. There is growing evidence that putrescine produced from arginine (Arg) and proline via ornithine decarboxylase is a key regulator of angiogenesis, embryogenesis, as well as placental and fetal growth. However, the underlying mechanisms are largely unknown. The present study tested the hypothesis that putrescine stimulates protein synthesis by activating the mechanistic target of rapamycin (mTOR) signaling pathway in porcine trophectoderm cell line 2 cells. The cells were cultured for 2 to 4 days in customized Arg-free Dulbecco modified Eagle Ham medium containing 0, 10, 25, or 50 μM putrescine or 100 μM Arg. Cell proliferation, protein synthesis, and degradation, as well as the abundance of total and phosphorylated mTOR, ribosomal protein S6 kinase 1, and eukaryotic initiation factor 4E-binding protein-1 (4EBP1), were determined. Our results indicate that putrescine promotes cell proliferation and protein synthesis in a dose- and time-dependent manner, which was inhibited by difluoro-methylornithine (an inhibitor of ornithine decarboxylase). Moreover, supplementation of culture medium with putrescine increased the abundance of phosphorylated mTOR and its downstream targets, 4EBP1 and p70 S6K1 proteins. Collectively, these findings reveal a novel and important role for putrescine in regulating the mTOR signaling pathway in porcine placental cells. We suggest that dietary supplementation with or intravenous administration of putrescine may provide a new and effective strategy to improve survival and growth of embryos/fetuses in mammals.
authors.affiliation: Department of Animal Science, Texas A&M University, College Station, Texas Hunan Provincial Engineering Research Center of Healthy Livestock and Key Laboratory of Agro-Ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, Hunan, China.
authors.forename: Xiangfeng
authors.initials: X
authors.lastname: Kong
authors.affiliation: Department of Animal Science, Texas A&M University, College Station, Texas.
authors.forename: Xiaoqiu
authors.initials: X
authors.lastname: Wang
authors.affiliation: Hunan Provincial Engineering Research Center of Healthy Livestock and Key Laboratory of Agro-Ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, Hunan, China.
authors.forename: Yulong
authors.initials: Y
authors.lastname: Yin
authors.affiliation: Department of Animal Science, Texas A&M University, College Station, Texas.
authors.forename: Xilong
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Animal Science, Texas A&M University, College Station, Texas.
authors.forename: Haijun
authors.initials: H
authors.lastname: Gao
authors.affiliation: Department of Animal Science, Texas A&M University, College Station, Texas.
authors.forename: Fuller W
authors.initials: FW
authors.lastname: Bazer
authors.affiliation: Department of Animal Science, Texas A&M University, College Station, Texas State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing, China g-wu@tamu.edu.
authors.forename: Guoyao
authors.initials: G
authors.lastname: Wu
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004475:Ectoderm / Q000187:drug effects* / Q000378:metabolism; D000518:Eflornithine / Q000494:pharmacology; D005260:Female; D011247:Pregnancy; D014176:Protein Biosynthesis / Q000187:drug effects*; D011700:Putrescine / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D013552:Swine; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D014327:Trophoblasts / Q000187:drug effects* / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D058570:TOR Serine-Threonine Kinases; D011700:Putrescine; D000518:Eflornithine
keywords: mTOR; placental cells; protein synthesis; putrescine