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Journal Article

Analysis of NOD2-mediated Proteome Response to Muramyl Dipeptide in HEK293 Cells

MPS-Authors

Weichart,  Dieter
Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons50168

Gobom,  Johan
Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society;

Gustavsson,  Niklas
Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons50409

Lehrach,  Hans
Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Weichart.pdf
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Citation

Weichart, D., Gobom, J., Klopfleisch, S., Häsler, R., Gustavsson, N., Billmann, S., et al. (2006). Analysis of NOD2-mediated Proteome Response to Muramyl Dipeptide in HEK293 Cells. Journal of Biological Chemistry, 281(4), 2380-2389. doi:10.1074/jbc.M505986200.


Cite as: http://hdl.handle.net/11858/00-001M-0000-0010-84C1-E
Abstract
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.