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Translational Control by Osmotically Active Solutes

渗透活性溶质的转化控制

基本信息

批准号：
9908062
负责人：
MARIA HATZOGLOU
金额：
$ 58.24万
依托单位：
CASE WESTERN RESERVE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-06-15 至 2022-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9908062
关键词：
Address Amino Acyl-tRNA Synthetases Apoptosis Apoptotic Attenuated Autophagocytosis Award Biochemical Bioinformatics Cell Cycle Progression Cell Nucleus Cell membrane Cells Cellular Stress Cessation of life Chronic Complex Cross-Linking Reagents Cysteine Cytoplasm Data Diabetes Mellitus Disease Electron Transport Complex III Endoplasmic Reticulum Epithelial Cells Evaluation Exposure to Genes Genetic Translation Genomics Grant High Pressure Liquid Chromatography IKKepsilon Immunoprecipitation In Vitro Inflammation Inflammatory Inflammatory Response Knock-in Malignant Neoplasms Manuscripts Measurement Mediating Membrane Membrane Proteins Messenger RNA Methodology Modification Mutation NADPH Oxidase NF-kappa B Nature Nerve Degeneration Nutritional Obesity Oxidative Stress Pathology Pathway interactions Phosphorylation Physiological Polyribosomes Post-Translational Protein Processing Protein Biosynthesis Proteins Proteomics Prothrombin Publishing RNA RNA Binding Reactive Oxygen Species Recombinants Recovery Regulation Ribosomes Role Science Signal Pathway Signal Transduction Small Nucleolar RNA Stress Symptoms Testing Therapeutic Time Transcriptional Regulation Transfer RNA Aminoacylation Translating Translations cell type corneal epithelium crosslink desensitization detection of nutrient endoplasmic reticulum stress follow-up genome-wide human disease in vitro activity intestinal epithelium mutant novel oxidation p65 polysome profiling protein complex reconstitution response solute trafficking transcriptome sequencing

项目摘要

The cellular response to nutritional and environmental stress has been associated with the pathology of many diseases. Major contributors to cell fate decisions in response to stress are: (i) cell-type specific factors, (ii) time and (iii) intensity of stress. Chronic and high intensity stress conditions attenuate survival and favor apoptosis. The best-studied physiological stress conditions that are related to human disease are endoplasmic reticulum (ER) stress, which is caused by the accumulation of unfolded proteins in the ER (diabetes, obesity, cancer) and oxidative stress, which results in increased reactive oxygen species (R08) and disruption of physiological R08 Signaling (neurodegeneration). Hypeosmotic stress is less-well studied. However, the major pathology with hyperosmotic stress is induction of the inflammatory response via increased expression of NF-kB target genes. The mechanisms that control inflammation and cellular recovery from hypeosmotic stress and specifically regulation of mRNA translation are not known. Because cells activate survival and apoptotic signals in response to stress, the interplay between these competing signals is crucial for elucidating adaptation and death mechanisms. We propose to study: 1. The functions of recently discovered cytoplasmic RNA-protein complexes in the response to hyperosmotic stress 2. Test the hypothesis that oxidation of cysteines drives HnRNPA 1 out of the nucleus during hyperosmotic stress and this cytoplasmic accumulation promotes apoptosis via translational control mechanisms. 3. The mechanisms of translational control during hyperosmotic stress. We propose a novel mechanism that controls ribosomal subunit availability and function that involves induction of autophagy 4. The mechanism via which the signaling of elF2α phosphorylation inhibits adaptation and promotes inflammatory mechanisms in response to hyperosmotic cells.

细胞对营养和环境压力的反应与