| Inflammatory macrophages induce NRF2 dependent proteasome activity in colonic NCM460 cells and thereby confer anti-apoptotic protection. | |
| | |
MedLine Citation:
|
PMID: 21990354 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
Adaptation of epithelial cells to persistent oxidative stress plays an important role in inflammation associated carcinogenesis. This adaptation process involves activation of Nuclear Factor-E2 related factor-2 (Nrf2) which has been recently shown to contribute to carcinogenesis through the induction of proteasomal gene expression and proteasome activity. To verify this possible link between inflammation, oxidative stress and Nrf2 dependent proteasome activation, we explored the impact of inflammatory (M1-) macrophages on the human colon epithelial cell line NCM460. Transwell cocultures with macrophages differentiated from granulocyte monocyte-colony stimulating factor (GM-CSF) treated monocytes led to an increased activity of Nrf2 in NCM460 cells along with an elevated proteasome activity. This higher proteasome activity resulted from Nrf2 dependent induction of proteasomal gene expression, as shown for the 19S- and 20S-subunit proteins S5a and α5, respectively. These effects of macrophage coculture were preceded by an increase of reactive oxygen species (ROS) in cocultured NCM460 cells and could be blocked by catalase or by the ROS scavenger Tiron, whereas transient treatment of NCM460 cells with H2O2 similarly led to Nrf2 dependent proteasome activation. Through the Nrf2 dependent increase of proteasomal gene expression and proteasome activity, the sensitivity of NCM460 cells to TRAIL or Irinotecan induced apoptosis declined. These findings indicate that inflammatory conditions such as the presence of M1-macrophages and the resulting oxidative stress are involved in the Nrf2 dependent gain of proteasome activity in epithelial cells, e.g. colonocytes, giving rise of greater resistance to apoptosis. This mechanism might contribute to inflammation associated carcinogenesis, e.g. of the colon. |
| | |
Authors:
|
Susanne Sebens; Iris Bauer; Claudia Geismann; Evelin Grage-Griebenow; Stefan Ehlers; Marie-Luise Kruse; Alexander Arlt; Heiner Schafer |
Related Documents
:
|
15205454 - Pseudomonas aeruginosa exotoxin a induces human mast cell apoptosis by a caspase-8 and ... 12388814 - The r1 subunit of herpes simplex virus ribonucleotide reductase protects cells against ... 21994614 - Antiviral properties of isg15. 15048704 - Frontline: induction of apoptosis and modulation of c-flipl and p53 in immature dendrit... 21037094 - Differential regulation of caspase-1 activation via nlrp3/nlrc4 inflammasomes mediated ... 16243064 - Toxicity of cationic lipid-dna complexes. |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2011-10-11 |
Journal Detail:
|
Title: The Journal of biological chemistry Volume: - ISSN: 1083-351X ISO Abbreviation: - Publication Date: 2011 Oct |
Date Detail:
|
Created Date: 2011-10-12 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
|
UKSH Campus Kiel, Germany; |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Inhibition of gluconeogenic genes by calcium-reglulated heat-stable protein-1 via repression of PPAR...
Next Document: {alpha}-Synuclein stimulates a dopamine transporter-dependent chloride current and modulates the act...