Proteomic investigation of urinary markers of carbon-tetrachloride-induced hepatic fibrosis in the Hanover Wistar rat.
Proteomic techniques such as two-dimensional gel electrophoresis (2-DGE) and mass spectrometry have become important tools for the identification of novel biomarkers of toxicity and disease. Ideally, such biomarkers need to be sensitive and organ specific, but, recently, it has become apparent that it would be an additional benefit to be able to measure biomarkers in samples obtained using non-invasive methods. The present study is concerned with the identification of novel urinary markers of hepatic fibrosis. In a carbon-tetrachloride-induced liver fibrosis rat model, analysis of urine by 2-DGE revealed an increase in the concentration of a number of proteins in animals with hepatic fibrosis. Using in-gel trypsin digest and nano-scale liquid chromatography combined with electrospray ionisation tandem mass spectrometry, protein spots were identified as copper/zinc superoxide dismutase, D: -dopachrome tautomerase, beta-2-microglobulin and neutrophil gelatinase associated lipocalin. These proteins are known to have important roles in the inflammatory response.
Smyth
Rosemary
R
Department of Pharmaceutical and Biological Chemistry, University of London, UK. rosemary.smyth@pharmacy.ac.uk
Lane
Catherine S
CS
Ashiq
Rukhsana
R
Turton
John A
JA
Clarke
Christopher J
CJ
Dare
Theo O
TO
York
Malcolm J
MJ
Griffiths
William
W
Munday
Michael R
MR
D000818:Animals; D015415:Biomarkers / Q000652:urine*; D002251:Carbon Tetrachloride / Q000633:toxicity*; D002853:Chromatography, Liquid; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D008103:Liver Cirrhosis / Q000139:chemically induced* / Q000652:urine; D040901:Proteomics; D051381:Rats; D017208:Rats, Wistar; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry
D015415:Biomarkers; D002251:Carbon Tetrachloride