Proteomic analysis of the renal effects of simulated occupational jet fuel exposure.
We analyzed protein expression in the cytosolic fraction prepared from whole kidneys in male Swiss-Webster mice exposed 1 h/day for five days to aerosolized JP-8 jet fuel at a concentration of 1000 mg/m3, simulating military occupational exposure. Kidney 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 changes in soluble kidney proteins resulted from jet fuel exposure. Several of the altered proteins were identified by peptide mass finger-printing and related to ultrastructural abnormalities, altered protein processing, metabolic effects, and paradoxical stress protein/detoxification system responses. These results demonstrate a significant but comparatively moderate JP-8 effect on protein expression in the kidney and provide novel molecular evidence of JP-8 nephrotoxicity. Human risk is suggested by these data but conclusive assessment awaits a noninvasive search for biomarkers in JP-8 exposed humans.
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
Lacey
M P
MP
Sun
Y
Y
Witten
M L
ML
Young
R S
RS
D000336:Aerosols; D000393:Air Pollutants / Q000633:toxicity*; D000401:Aircraft; D000626:Aminopeptidases / Q000378:metabolism; D000818:Animals; D003598:Cytoskeletal Proteins; D015180:Electrophoresis, Gel, Two-Dimensional; D006609:High Mobility Group Proteins / Q000378:metabolism; D007648:Kerosene / Q000633:toxicity; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D007674:Kidney Diseases / Q000139:chemically induced*; D008297:Male; D051379:Mice; D016273:Occupational Exposure; D020652:Peptide Elongation Factor 2 / Q000378:metabolism; D010578:Petroleum / Q000633:toxicity*; D010750:Phosphoproteins / Q000378:metabolism; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D011506:Proteins / Q000032:analysis / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014335:Tropomyosin / Q000378:metabolism; D000099149:Ezrin
D000336:Aerosols; D000393:Air Pollutants; D000626:Aminopeptidases; D003598:Cytoskeletal Proteins; D006609:High Mobility Group Proteins; D007648:Kerosene; D020652:Peptide Elongation Factor 2; D010578:Petroleum; D010750:Phosphoproteins; D010751:Phosphopyruvate Hydratase; D011506:Proteins; D014335:Tropomyosin; D000099149:Ezrin