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Regulation of Protein Synthesis in Neonatal Sepsis

新生儿败血症中蛋白质合成的调节

基本信息

批准号：
7413468
负责人：
RENAN A ORELLANA
金额：
$ 12.29万
依托单位：
BAYLOR COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-05-01 至 2010-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7413468
关键词：
3-Phosphoinositide Dependent Protein Kinase-1 Acute Address Adult Affect Amino Acids Animals Binding Child Complex Condition Critical Illness Development Dose Endotoxemia Endotoxins Equilibrium Eukaryotic Initiation Factors Exhibits Family suidae Growth Hindlimb Hormonal Hormones Infant Inflammatory Insulin Knowledge Lead Lipopolysaccharides Measurement Measures Medical Messenger RNA Metabolic Metabolism Methods Muscle Muscle Proteins NF-kappa B Neonatal Newborn Animals Newborn Infant Nutrient Nutritional Organism Pathway interactions Peptide Initiation Factors Phosphorylation Phosphotransferases Predisposition Process Protein Biosynthesis Proteolysis Proto-Oncogene Proteins c-akt Rate Recovery Regulation Reporting Sepsis Signal Transduction Supplementation Sus scrofa Techniques Tracer Translation Initiation day feeding human TYRP1 protein in vivo mature animal neonate novel protein degradation protein metabolism research study response septic

项目摘要

DESCRIPTION (provided by applicant): The susceptibility of the neonate for nutritional depletion during illness, and its opposed metabolic ability to utilize nutrients efficiently for growth offers a novel paradigm to evaluate nutrient-hormonal interactions during sepsis. Our long-term objectives are to identify the fundamental mechanisms that regulate amino acid use, including the interaction of hormones, nutrients, and development, in inflammatory conditions such as sepsis. In this proposal, we intend to analyze the pathways that regulate amino acid metabolism in septic neonates. In Aim 1, we hypothesize that raising amino acids in endotoxemic neonates enhances muscle protein synthesis rates. Thus, amino acid dose response studies will be performed in endotoxin (LPS) infused 7- and 26-day-old pigs by using hormone-substrate clamp techniques and in vivo measurement of protein synthesis with isotopic tracer methods. In Aim 2, we wish to determine whether amino acids influence muscle protein synthesis in LPS-infused neonates by affecting activation of translation initiation factors involved in the binding of mRNA, but not met-tRNAi, to the 40S ribosomal complex. Consequently, we will measure in muscle eukaryotic initiation factor (elF) 2B activity, the phosphorylation of eIF4E, 4E-BP1, p70S6 kinase and protein kinase B (PKB), the association of eIF4E with eIF4G and 4E-BP1, and the activation of NFkappaB signaling. In Aim 3, we wish to determine whether muscle proteolysis is enhanced by sepsis in neonates and whether the rate of proteolysis can be suppressed by administration of insulin. Therefore, LPS-infused 7- and 26-day-old pigs subjected to hormone-substrate clamps will be examined using a stable isotopic tracer/mass transorgan balance technique to quantify protein degradation in the hindlimb in the presence of different concentrations of insulin. Knowledge of the nutrient-hormone interface during a critical illness and their developmental distinctiveness can help characterize and optimize the medical management towards recovery and reestablishment of adequate growth after infants and children have been acutely ill.

描述（由申请人提供）：