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          Institute: MPI für molekulare Genetik     Collection: Department of Vertebrate Genomics     Display Documents

ID: 313022.0, MPI für molekulare Genetik / Department of Vertebrate Genomics
Analysis of NOD2-mediated Proteome Response to Muramyl Dipeptide in HEK293 Cells
Authors:Weichart, Dieter; Gobom, Johan; Klopfleisch, Sina; Häsler, Robert; Gustavsson, Niklas; Billmann, Susanne; Lehrach, Hans; Seegert, Dirk; Schreiber, Stefan; Rosenstiel, Philip
Date of Publication (YYYY-MM-DD):2006-01-27
Title of Journal:Journal of Biological Chemistry
Journal Abbrev.:J Biol Chem
Issue / Number:4
Start Page:2380
End Page:2389
Copyright:© 2006 by the American Society for Biochemistry and Molecular Biology
Review Status:not specified
Audience:Experts Only
Abstract / Description:NOD2, a cytosolic receptor for the bacterial proteoglycan fragment muramyl dipeptide (MDP), plays an important role in the recognition of intracellular pathogens. Variants in the bacterial sensor domain of NOD2 are genetically associated with an increased risk for the development of Crohn disease, a human chronic inflammatory bowel disease. In the present study, global protein expression changes after MDP stimulation were analyzed by two-dimensional PAGE of total protein extracts of human cultured cells stably transfected with expression constructs encoding for wild type NOD2 (NOD2WT) or the disease-associated NOD2 L1007fsinsC (NOD2SNP13) variant. Differentially regulated proteins were identified by matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) peptide mass fingerprinting and MALDI MS/MS. The limited overlap in the responses of the NOD2-overexpressing cell lines to MDP included a down-regulation of heat shock 70-kDa protein 4. A complex pro-inflammatory program regulated by NOD2WT that encompasses a regulation of key genes involved in protein folding, DNA repair, cellular redox homeostasis, and metabolism was observed both under normal growth conditions and after stimulation with MDP. By using the comparison of NOD2WT and disease-associated NOD2SNP13 variant, we have identified a proteomic signature pattern that may further our understanding of the influence of genetic variations in the NOD2 gene in the pathophysiology of chronic inflammatory bowel disease.
Comment of the Author/Creator:e-mail: s.schreiber@mucosa.de
External Publication Status:published
Document Type:Article
Communicated by:Hans Lehrach
Affiliations:MPI für molekulare Genetik
External Affiliations:Institute of Clinical Molecular Biology, University Hospital Schleswig-Holstein, D-24105 Kiel and Conaris Research Institute AG, D-24105 Kiel, Germany
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