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Protein Kinase R Mediates the Inflammatory Response Induced by Hyperosmotic Stress
- Source :
- Molecular and cellular biology. 37(4)
- Publication Year :
- 2016
-
Abstract
- High extracellular osmolarity results in a switch from an adaptive to an inflammatory gene expression program. We show that hyperosmotic stress activates the protein kinase R (PKR) independently of its RNA-binding domain. In turn, PKR stimulates nuclear accumulation of nuclear factor κB (NF-κB) p65 species phosphorylated at serine-536, which is paralleled by the induction of a subset of inflammatory NF-κB p65-responsive genes, including inducible nitric oxide synthase (iNOS), interleukin-6 (IL-6), and IL-1β. The PKR-mediated hyperinduction of iNOS decreases cell survival in mouse embryonic fibroblasts via mechanisms involving nitric oxide (NO) synthesis and posttranslational modification of proteins. Moreover, we demonstrate that the PKR inhibitor C16 ameliorates both iNOS amplification and disease-induced phenotypic breakdown of the intestinal epithelial barrier caused by an increase in extracellular osmolarity induced by dextran sodium sulfate (DSS) in vivo. Collectively, these findings indicate that PKR activation is an essential part of the molecular switch from adaptation to inflammation in response to hyperosmotic stress.
- Subjects :
- 0301 basic medicine
Osmotic shock
Nitrosation
Nitric Oxide Synthase Type II
Inflammation
Apoptosis
Biology
Nitric Oxide
Nitric oxide
03 medical and health sciences
chemistry.chemical_compound
eIF-2 Kinase
Osmotic Pressure
medicine
Extracellular
Animals
RNA, Messenger
Phosphorylation
Molecular Biology
RNA, Double-Stranded
Osmotic concentration
Transcription Factor RelA
Cell Biology
Colitis
Protein kinase R
Molecular biology
Nitric oxide synthase
Enzyme Activation
Mice, Inbred C57BL
030104 developmental biology
Enterocytes
Phenotype
chemistry
biology.protein
medicine.symptom
Research Article
Subjects
Details
- ISSN :
- 10985549
- Volume :
- 37
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Molecular and cellular biology
- Accession number :
- edsair.doi.dedup.....057e4c227ff6813dfec5dd6d7e535a29