Proteomic analysis of simulated occupational jet fuel exposure in the lung.
We analyzed protein expression in the cytosolic fraction prepared from whole lung tissue in male Swiss-Webster mice exposed 1 h/day for seven days to aerosolized JP-8 jet fuel at concentrations of 1000 and 2500 mg/m3, simulating military occupational exposure. Lung cytosol samples were solubilized and separated via large scale, high resolution two-dimensional electrophoresis (2-DE) and gel patterns scanned, digitized and processed for statistical analysis. Significant quantitative and qualitative changes in tissue cytosol proteins resulted from jet fuel exposure. Several of the altered proteins were identified by peptide mass fingerprinting, confirmed by sequence tag analysis, and related to impaired protein synthetic machinery, toxic/metabolic stress and detoxification systems, ultrastructural damage, and functional responses to CO2 handling, acid-base homeostasis and fluid secretion. These results demonstrate a significant but comparatively moderate JP-8 effect on protein expression and corroborate previous morphological and biochemical evidence. Further molecular marker development and mechanistic inferences from these observations await proteomic analysis of whole tissue homogenates and other cell compartment, i.e., mitochondria, microsomes, and nuclei of lung and other targets.
Witzmann
F A
FA
Department of Biology, Indiana University-Purdue University, Columbus 47203, USA. fwitzman@iupui.edu
Bauer
M D
MD
Fieno
A M
AM
Grant
R A
RA
Keough
T W
TW
Kornguth
S E
SE
Lacey
M P
MP
Siegel
F L
FL
Sun
Y
Y
Wright
L S
LS
Young
R S
RS
Witten
M L
ML
D000818:Animals; D015180:Electrophoresis, Gel, Two-Dimensional; D006838:Hydrocarbons / Q000633:toxicity*; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron; D016273:Occupational Exposure; D011506:Proteins / Q000302:isolation & purification; D020543:Proteome; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D006838:Hydrocarbons; D011506:Proteins; D020543:Proteome