Analysis of NOD2-mediated proteome response to muramyl dipeptide in HEK293 cells
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/951868
- author
- Weichart, D ; Gobom, J ; Klopfleisch, S ; Hasler, R ; Gustavsson, Niklas LU ; Billmann, S ; Lehrach, H ; Seegert, D ; Schreiber, S and Rosenstiel, P
- organization
- publishing date
- 2006
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Biological Chemistry
- volume
- 281
- issue
- 4
- pages
- 2380 - 2389
- publisher
- American Society for Biochemistry and Molecular Biology
- 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
- 2022-03-30 22:45:19
@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 = {{American Society for Biochemistry and Molecular Biology}},
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}},
}