Comparative proteomic analysis of cysteine oxidation in colorectal cancer patients
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Oxidative stress promotes damage to cellular proteins, lipids, membranes and DNA, and plays a key role in the development of cancer. Reactive oxygen species disrupt redox homeostasis and promote tumor formation by initiating aberrant activation of signaling pathways that lead to tumorigenesis. We used shotgun proteomics to identify proteins containing oxidation-sensitive cysteines in tissue specimens from colorectal cancer patients. We then compared the patterns of cysteine oxidation in the membrane fractions between the tumor and non-tumor tissues. Using nano-UPLC-MSE proteomics, we identified 31 proteins containing 37 oxidation-sensitive cysteines. These proteins were observed with IAM-binding cysteines in non-tumoral region more than tumoral region of CRC patients. Then using the Ingenuity pathway program, we evaluated the cellular canonical networks connecting those proteins. Within the networks, proteins with multiple connections were related with organ morphology, cellular metabolism, and various disorders. We have thus identified networks of proteins whose redox status is altered by oxidative stress, perhaps leading to changes in cellular functionality that promotes tumorigenesis.
Keywordscolorectal cancer cysteine oxidation iodoacetamide protein network shotgun proteomics
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- Brennan, J.P., Wait, R., Begum, S., Bell, J.R., Dunn, M.J., and Eaton, P. (2004). Detection and mapping of widespread intermolecular protein disulfide formation during cardiac oxidative stress using proteomics with diagonal electrophoresis. J. Biol. Chem. 279, 41352–41360.PubMedCrossRefGoogle Scholar
- Domokos, M., Jakus, J., Szeker, K., Csizinszky, R., Csiko, G., Neogrady, Z., Csordas, A., and Galfi, P. (2010). Butyrate-induced cell death and differentiation are associated with distinct patterns of ROS in HT29-derived human colon cancer cells. Dig. Dis. Sci. 55, 920–930.PubMedCrossRefGoogle Scholar
- Kitz, K., Windischhofer, W., Leis, H.J., Huber, E., Kollroser, M., and Malle, E. (2011). 15-Deoxy-Delta12,14-prostaglandin J2 induces Cox-2 expression in human osteosarcoma cells through MAPK and EGFR activation involving reactive oxygen species. Free Radic. Biol. Med. 50, 854–865.PubMedCrossRefGoogle Scholar
- Olivieri, G., Novakovic, M., Savaskan, E., Meier, F., Baysang, G., Brockhaus, M., and Muller-Spahn, F. (2002). The effects of beta-estradiol on SHSY5Y neuroblastoma cells during heavy metal induced oxidative stress, neurotoxicity and beta-amyloid secretion. Neuroscience 113, 849–855.PubMedCrossRefGoogle Scholar
- Pamplona, R., Dalfo, E., Ayala, V., Bellmunt, M.J., Prat, J., Ferrer, I., and Portero-Otin, M. (2005). Proteins in human brain cortex are modified by oxidation, glycoxidation, and lipoxidation. Effects of Alzheimer disease and identification of lipoxidation targets. J. Biol. Chem. 280, 21522–21530.PubMedCrossRefGoogle Scholar
- Phalen, T.J., Weirather, K., Deming, P.B., Anathy, V., Howe, A.K., van der Vliet, A., Jonsson, T.J., Poole, L.B., and Heintz, N.H. (2006). Oxidation state governs structural transitions in peroxiredoxin II that correlate with cell cycle arrest and recovery. J. Cell Biol. 175, 779–789.PubMedCrossRefGoogle Scholar
- Saaf, A.M., Halbleib, J.M., Chen, X., Yuen, S.T., Leung, S.Y., Nelson, W.J., and Brown, P.O. (2007). Parallels between global transcriptional programs of polarizing Caco-2 intestinal epithelial cells in vitro and gene expression programs in normal colon and colon cancer. Mol. Biol. Cell 18, 4245–4260.PubMedCrossRefGoogle Scholar
- Werth, C., Stuhlmann, D., Cat, B., Steinbrenner, H., Alili, L., Sies, H., and Brenneisen, P. (2008). Stromal resistance of fibroblasts against oxidative damage: involvement of tumor cell-secreted platelet-derived growth factor (PDGF) and phosphoinositide 3-kinase (PI3K) activation. Carcinogenesis 29, 404–410.PubMedCrossRefGoogle Scholar