Document Detail


N-carbamylglutamate enhances pregnancy outcome in rats through activation of the PI3K/PKB/mTOR signaling pathway.
MedLine Citation:
PMID:  22848442     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Administration of N-carbamylglutamate (NCG), an analogue of endogenous N-acetyl-glutamate (an activator of arginine synthesis) has been shown to enhance neonatal growth by increasing circulating arginine levels. However, the effect of NCG on pregnancy remains unknown. This study examined the effects of NCG on pregnancy outcome and evaluated potential mechanisms involved. Reproductive performance, embryo implantation, and concentration of amino acids in serum and uterine flushing, were determined in rats fed control or NCG supplemented diets. Ishikawa cells and JAR cells were used to examine the mechanism by which NCG affects embryo implantation. Dietary NCG supplementation increased serum levels of arginine, onithine, and proline, as well as uterine levels of arginine, glutamine, glutamate, and proline. Additionally, it stimulated LIF expression, and enhanced the activation of signal transduction and activator of transcription 3 (Stat3), protein kinase B (PKB), and 70-kDa ribosomal protein S6 kinase (S6K1) during the periimplantation period, resulting in an increase in litter size but not birth weight. In uterine Ishikawa cells, LIF expression was also enhanced by treatment with arginine and its metabolites. In trophoblast JAR cells, treatment with arginine and its metabolites enhanced Stat3, PKB, and S6K1 activation and facilitated cellular adhesion activity. These effects were abolished by pretreatment with inhibitors of phosphatidylinositol 3-kinase (wortmannin) and mammalian target of rapamycin (rapamycin). The results demonstrate that NCG supplementation enhances pregnancy outcome and have important implications for the pregnancy outcome of mammalian species.
Authors:
Xiangfang Zeng; Zhimin Huang; Xiangbing Mao; Junjun Wang; Guoyao Wu; Shiyan Qiao
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-07-27
Journal Detail:
Title:  PloS one     Volume:  7     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2012  
Date Detail:
Created Date:  2012-07-31     Completed Date:  2013-03-11     Revised Date:  2013-07-12    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e41192     Citation Subset:  IM    
Affiliation:
State Key Laboratory of Animal Nutrition, China Agricultural University, Beijing, China.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Adhesion / drug effects
Dietary Supplements*
Embryo Implantation / drug effects*
Female
Glutamates / pharmacology*
Leukemia Inhibitory Factor / biosynthesis
Live Birth*
Phosphatidylinositol 3-Kinases / metabolism*
Pregnancy / drug effects,  physiology
Proto-Oncogene Proteins c-akt / metabolism*
Rats
Rats, Sprague-Dawley
Ribosomal Protein S6 Kinases / metabolism
STAT3 Transcription Factor / metabolism
TOR Serine-Threonine Kinases / metabolism*
Trophoblasts / metabolism
Chemical
Reg. No./Substance:
0/Glutamates; 0/Leukemia Inhibitory Factor; 0/STAT3 Transcription Factor; 0/Stat3 protein, rat; 1188-38-1/N-carbamylglutamate; EC 2.7.1.-/Phosphatidylinositol 3-Kinases; EC 2.7.1.1/TOR Serine-Threonine Kinases; EC 2.7.1.1/mTOR protein, rat; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 2.7.11.1/Ribosomal Protein S6 Kinases; EC 2.7.11.1/S6K1 protein, rat
Comments/Corrections

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