title: Complementary proteomic approaches reveal mitochondrial dysfunction, immune and inflammatory dysregulation in a mouse model of Gulf War Illness.
abstract: 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.
  
  
  
  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. 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.
authors.affiliation: Department of Genomics, The Roskamp Institute, Sarasota, FL, USA.|Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Zuchra
authors.identifier: 0000-0002-5728-0563
authors.initials: Z
authors.lastname: Zakirova
authors.affiliation: Department of Genomics, The Roskamp Institute, Sarasota, FL, USA.|Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA.
authors.forename: Jon
authors.initials: J
authors.lastname: Reed
authors.affiliation: Department of Genomics, The Roskamp Institute, Sarasota, FL, USA.
authors.forename: Gogce
authors.initials: G
authors.lastname: Crynen
authors.affiliation: Department of Genomics, The Roskamp Institute, Sarasota, FL, USA.
authors.forename: Lauren
authors.initials: L
authors.lastname: Horne
authors.affiliation: Department of Genomics, The Roskamp Institute, Sarasota, FL, USA.|University of Central Florida College of Medicine, Orlando, FL, USA.
authors.forename: Samira
authors.initials: S
authors.lastname: Hassan
authors.affiliation: Department of Genomics, The Roskamp Institute, Sarasota, FL, USA.
authors.forename: Venkatarajan
authors.initials: V
authors.lastname: Mathura
authors.affiliation: Department of Genomics, The Roskamp Institute, Sarasota, FL, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Mullan
authors.affiliation: Department of Genomics, The Roskamp Institute, Sarasota, FL, USA.|James A. Haley Veterans Hospital, Tampa, FL, USA.
authors.forename: Fiona
authors.initials: F
authors.lastname: Crawford
authors.affiliation: Department of Genomics, The Roskamp Institute, Sarasota, FL, USA.|James A. Haley Veterans Hospital, Tampa, FL, USA.
authors.forename: Ghania
authors.initials: G
authors.lastname: Ait-Ghezala
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D007249:Inflammation / Q000150:complications; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000473:pathology*; D018923:Persian Gulf Syndrome / Q000150:complications / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D040901:Proteomics
chemical_list: D016207:Cytokines
keywords: Gulf War; MS/MS; SIDL; iTRAQ; mitochondrial dysfunction