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Complementary proteomic approaches reveal mitochondrial dysfunction, immune and inflammatory dysregulation in a mouse model of Gulf War Illness
- Source :
- Proteomics. Clinical Applications
- Publication Year :
- 2017
- Publisher :
- Wiley, 2017.
-
Abstract
- Purpose Long-term consequences of combined pyridostigmine bromide (PB) and permethrin (PER) exposure in C57BL6/J mice using a well-characterized mouse model of exposure to these Gulf War (GW) agents were explored at the protein level. Experimental design We used orthogonal proteomic approaches to identify pathways that are chronically impacted in the mouse CNS due to semiacute GW agent exposure early in life. These analyses were performed on soluble and membrane-bound protein fractions from brain samples using two orthogonal isotopic labeling LC-MS/MS proteomic approaches—stable isotope dimethyl labeling and iTRAQ. Results The use of these approaches allowed for greater coverage of proteins than was possible by either one alone and revealed both distinct and overlapping datasets. This combined analysis identified changes in several mitochondrial, as well as immune and inflammatory pathways after GW agent exposure. Conclusions and clinical relevance The work discussed here provides insight into GW agent exposure dependent mechanisms that adversely affect mitochondrial function and immune and inflammatory regulation. Collectively, our work identified key pathways which were chronically impacted in the mouse CNS following acute GW agent exposure, this may lead to the identification of potential targets for therapeutic intervention in the future. Long-term consequences of combined PB and PER exposure in C57BL6/J mice using a well-characterized mouse model of exposure to these GW agents were explored at the protein level. Expanding on earlier work, we used orthogonal proteomic approaches to identify pathways that are chronically impacted in the mouse CNS due to semiacute GW agent exposure early in life. These analyses were performed on soluble and membrane-bound protein fractions from brain samples using two orthogonal isotopic labeling LC-MS/MS proteomic approaches—stable isotope dimethyl labeling and iTRAQ. The use of these approaches allowed for greater coverage of proteins than was possible by either one alone and revealed both distinct and overlapping datasets. This combined analysis identified changes in several mitochondrial, as well as immune and inflammatory pathways after GW agent exposure. The work discussed here provides insight into GW agent exposure dependent mechanisms that adversely affect mitochondrial function and immune and inflammatory regulation at 5 months postexposure to PB + PER.
- Subjects :
- Male
Proteomics
0301 basic medicine
Pathology
medicine.medical_specialty
Clinical Biochemistry
Pharmacology
Biology
Gulf war
Mice
03 medical and health sciences
0302 clinical medicine
Immune system
mitochondrial dysfunction
MS/MS
medicine
Animals
Persian Gulf Syndrome
Research Articles
SIDL
Inflammation
Protein level
Gulf War
Mitochondria
Mice, Inbred C57BL
Disease Models, Animal
030104 developmental biology
iTRAQ
Cytokines
Inflammatory pathways
Pyridostigmine Bromide
030217 neurology & neurosurgery
Function (biology)
Research Article
Subjects
Details
- ISSN :
- 18628354 and 18628346
- Volume :
- 11
- Database :
- OpenAIRE
- Journal :
- PROTEOMICS – Clinical Applications
- Accession number :
- edsair.doi.dedup.....1cf33ee29bc483f5e7c63aa6760bac23