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Analysis of NOD2-mediated proteome response to muramyl dipeptide in HEK293 cells

Weichart, D ; Gobom, J ; Klopfleisch, S ; Hasler, R ; Gustavsson, Niklas LU ; Billmann, S ; Lehrach, H ; Seegert, D ; Schreiber, S and Rosenstiel, P (2006) In Journal of Biological Chemistry 281(4). p.2380-2389
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 (NOD2(WT)) or the disease-associated NOD2 L1007fsinsC (NOD2(SNP13)) variant. Differentially regulated proteins were identified by matrix-assisted laser desorption... (More)
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 (NOD2(WT)) or the disease-associated NOD2 L1007fsinsC (NOD2(SNP13)) 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 NOD2(WT) 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 NOD2(WT) and disease-associated NOD2(SNP13) 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. (Less)
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author
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publishing date
type
Contribution to journal
publication status
published
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in
Journal of Biological Chemistry
volume
281
issue
4
pages
2380 - 2389
publisher
ASBMB
external identifiers
  • scopus:33644871640
ISSN
1083-351X
DOI
10.1074/jbc.M505986200
language
English
LU publication?
yes
id
b0f4abf2-fa0d-4468-9847-5d87dba5b9aa (old id 951868)
date added to LUP
2016-04-04 07:48:44
date last changed
2020-04-22 03:39:51
@article{b0f4abf2-fa0d-4468-9847-5d87dba5b9aa,
  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 (NOD2(WT)) or the disease-associated NOD2 L1007fsinsC (NOD2(SNP13)) 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 NOD2(WT) 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 NOD2(WT) and disease-associated NOD2(SNP13) 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.},
  author       = {Weichart, D and Gobom, J and Klopfleisch, S and Hasler, R and Gustavsson, Niklas and Billmann, S and Lehrach, H and Seegert, D and Schreiber, S and Rosenstiel, P},
  issn         = {1083-351X},
  language     = {eng},
  number       = {4},
  pages        = {2380--2389},
  publisher    = {ASBMB},
  series       = {Journal of Biological Chemistry},
  title        = {Analysis of NOD2-mediated proteome response to muramyl dipeptide in HEK293 cells},
  url          = {http://dx.doi.org/10.1074/jbc.M505986200},
  doi          = {10.1074/jbc.M505986200},
  volume       = {281},
  year         = {2006},
}