Proteomic analysis of iron overload in human hepatoma cells.
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, 21 spots 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.
Petrak
Jiri
J
Institute of Hematology and Blood Transfusion, U Nemocnice 1, Prague, Czech Republic. petra@uhkt.cz
Myslivcova
Denisa
D
Man
Petr
P
Cmejla
Radek
R
Cmejlova
Jana
J
Vyoral
Daniel
D
D000444:Aldehyde Dehydrogenase / Q000235:genetics; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000595:Amino Acid Sequence; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D015180:Electrophoresis, Gel, Two-Dimensional; D020869:Gene Expression Profiling; D006801:Humans; D019190:Iron Overload / Q000378:metabolism*; D015227:Lipid Peroxidation; D008099:Liver / Q000378:metabolism*; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D018384:Oxidative Stress; D040901:Proteomics / Q000379:methods*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods
C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial