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Am J Physiol Gastrointest Liver Physiol 290: G1059-G1066, 2006. First published January 12, 2006; doi:10.1152/ajpgi.00469.2005
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INNOVATIVE METHODOLOGY

Proteomic analysis of iron overload in human hepatoma cells

Jiri Petrak,1 Denisa Myslivcova,1 Petr Man,2 Radek Cmejla,1 Jana Cmejlova,1 and Daniel Vyoral1,3

1Institute of Hematology and Blood Transfusion, 2Institute of Microbiology, Czech Academy of Sciences, and 3Institute of Pathophysiology, First Medical Faculty, Charles University, Prague, Czech Republic

Submitted 6 October 2005 ; accepted in final form 3 January 2006

Iron-mediated organ damage is common in patients with iron overload diseases, namely, hereditary hemochromatosis. Massive iron deposition in parenchymal organs, particularly in the liver, causes organ dysfunction, fibrosis, cirrhosis, and also hepatocellular carcinoma. To obtain deeper insight into the poorly understood and complex cellular response to iron overload and consequent oxidative stress, we studied iron overload in liver-derived HepG2 cells. Human hepatoma HepG2 cells were exposed to a high concentration of iron for 3 days, and protein expression changes initiated by the iron overload were studied by two-dimensional electrophoresis and mass spectrometry. From a total of 1,060 spots observed, 21spots were differentially expressed by iron overload. We identified 19 of them; 11 identified proteins were upregulated, whereas 8 identified proteins showed a decline in response to iron overload. The differentially expressed proteins are involved in iron storage, stress response and protection against oxidative stress, protein folding, energy metabolism, gene expression, cell cycle regulation, and other processes. Many of these molecules have not been previously suggested to be involved in the response to iron overload and the consequent oxidative stress.

liver; proteomics



Address for reprint requests and other correspondence: J. Petrak, Institute of Hematology and Blood Transfusion, U Nemocnice 1, Prague, Czech Republic (e-mail: petra{at}uhkt.cz)




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J. Petrak, D. Myslivcova, P. Man, R. Cmejla, J. Cmejlova, D. Vyoral, M. Elleder, and C. D. Vulpe
Proteomic analysis of hepatic iron overload in mice suggests dysregulation of urea cycle, impairment of fatty acid oxidation, and changes in the methylation cycle
Am J Physiol Gastrointest Liver Physiol, June 1, 2007; 292(6): G1490 - G1498.
[Abstract] [Full Text] [PDF]




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