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Project 3: Cellular Effects of Aldehydic Products of Lipid Peroxidation

项目3：脂质过氧化醛产物的细胞效应

基本信息

批准号：
8106389
负责人：
LAWRENCE J. MARNETT
金额：
$ 30.95万
依托单位：
VANDERBILT UNIVERSITY
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：
2005-09-12 至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/8106389
关键词：
4 hydroxynonenal Affect Agonist Aldehydes Alkynes Anti-Inflammatory Agents Anti-inflammatory Arts Biochemical Biological Biological Assay Biology Cell Line Cell physiology Cells Chemicals Chemistry DNA DNA Damage Data Set Disease Equipment and supply inventories Gene Expression Genetic Transcription Genomics Glutathione Glycerophospholipids Goals Health Human Hydrogen Peroxide Individual Inflammation Inflammatory Inflammatory Response Interferon Type II Laboratories Lead Lipid Chemistry Lipid Peroxidation Lipids Lipopolysaccharides Luciferases Mass Spectrum Analysis Mediator of activation protein Microarray Analysis Modeling Modification Mutagenesis Nonesterified Fatty Acids Outcome Oxidants Pathway Analysis Pathway interactions Pattern Phosphotransferases Physiological Post-Translational Protein Processing Proteins Proteomics RNA Reagent Reporter Research Research Personnel Resources Role Series Signal Pathway Signal Transduction Small Interfering RNA Stress System TP53 gene Technology Testing Toxic effect Toxicity Tests base cytotoxic human disease interest link protein macrophage novel strategies oxidation programs protein expression protein profiling research study response thioredoxin reductase tool transcription factor uptake vector

项目摘要

Emerging evidence from several laboratories indicates that lipid oxidation products make major contributions to human disease. An important class of lipid oxidation products are electrophiles that react with cellular nucleophiles including glutathione, proteins, and DNA. Although glutathione and DMA modification has been studied for many years, inadequate technology has limited our ability to investigate protein modification and its relation to biological outcome. Technological advances in proteomics and genomics now make it possible to assemble comprehensive profiles of proteins modified by lipid electrophiles as well as the transcriptional changes they induce. Comparison of these dense datasets using systems approaches enables hypotheses to be generated linking protein modification to cellular response. Research in the Program Project over the past two years has generated critical reagents and novel approaches for identifying lipid electrophilemodified proteins and their biological consequences. We are now poised to mount an aggressive campaign to define the chemistry and biology of protein modification by lipid electrophiles and its relationship to inflammation, a major contributor to many human diseases. The role of Project 3 is to identify the most biologically interesting lipid electrophiles emanating from research in Projects 1 and.2 and to define the transcriptional changes that they induce in the human macrophage cell line, THP-1. This information will be compared to the pattern of protein modification by the same agents, which will be determined in Project 4, and hypotheses formulated linking protein modification to biological outcome. These hypotheses will be tested using a combination of approaches such as RNA knockdown, ectopic protein expression, and biochemical assays. This will enable the elucidation of mechanisms by which protein modifications by lipid lectrophiles lead to pro- and anti-inflammatory responses.

来自几个实验室的新证据表明，脂质氧化产物起主要作用