Abstract
Lung tissue is exposed to higher concentrations of oxygen than most other tissues. In addition, cigarette smoke and environmental toxic particles not only contain reactive oxygen species (ROS), but also enhance ROS production and activate various oxidant generating mechanisms in the cell. ROS include a number of highly reactive oxygen (superoxide radical O2 - hydrogen peroxide H2O2, hydroxyl radical OH) and nitrogen (nitric oxide NO, peroxynitrite ONOO) metabolites (1). At low concentrations, ROS may play a fundamental role in the regulation of signal transduction (2), but persistent oxidant exposure can also cause injury to almost all cellular components, including membrane lipids and the genetic material of the cell. ROS also appear to play an important role in cancer biology, carcinogenesis, tumor growth, and drug therapy. Many aspects of ROS mechanisms in these pathways remain unsolved, but it has been hypothesized that antioxidant enzymes may play a role in the proliferation and apoptosis of cancer cells, and in the resistance of malignant cells to chemotherapeutic agents and radiation (3-5).
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Halliwell, B. (1991) Reactive oxygen species in living systems: source, biochemistry, and role in human disease. Am. J. Med. 91, 14S–22S.
Thannickal, V. J. and Fanburg, B. L. (2000) Reactive oxygen species in cell signaling. Am. J. Physiol. Lung Cell Mol. Physiol. 279, L1005–L1028.
Tew, K. D. (1994) Glutathione-associated enzymes in anticancer drug resistance. Cancer Res. 54, 4313–4320.
Zhang, K., Mack, P., and Wong, K. P. (1998) Glutathione-related mechanisms in cellular resistance to anticancer drugs. Int. J. Oncol. 12, 871–882.
O'Brien, M. L. and Tew, K. D. (1996) Glutathione and related enzymes in multidrug resistance. Eur. J. Cancer 32A, 967–978.
Halliwell, B. and Gutteridge, J. M. C. (1996) Free Radicals in Biology and Medicine. Oxford University Press, New York, NY.
Holmgren, A. (1985) Thioredoxin. Annu. Rev. Biochem. 54, 237–271.
Powis, G., Mustacich, D., and Coon, A. (2000) The role of the redox protein thioredoxin in cell growth and cancer. Free Radic. Biol. Med. 29, 312–322.
Rhee, S. G. (1999) Redox signaling: hydrogen peroxide as intracellular messenger. Exp. Mol. Med. 31, 53–59.
Tipnis, S. R., Blake, D. G., Shepherd, A. G., and McLellan, L. I. (1999) Overexpression of the regulatory subumit of γ-glutamylcysteine synthetase in HeLa cells increases γ-glutamylcysteine synthetase activity and confers drug resistance. Biochem. J. 337, 559–566.
Kinnula, V. L., Yankaskas, J. R., Chang, L., Virtanen, I., Linnala, A., Kang, B. H., and Crapo, J. D. (1994) Primary and immortalized (BEAS 2B) human bronchial epithelial cells have significant antioxidative capacity in vitro. Am. J. Respir. Cell Mol. Biol. 11, 568–576.
Erzurum, S. C., Danel, C., Gillissen, A., Chu, C. S., Trapnell, B. C., and Crystal, R. G. (1993) In vivo antioxidant gene expression in human airway epithelium of normal individuals exposed to 100% O2. J. Appl. Physiol. 75, 1256–1262.
Cantin, A. M., North, S. L., Hubbard, R. C., and Crystal, R. G. (1987) Normal alveolar epithelial lining fluid contains high levels of glutathione. J. Appl. Physiol. 63, 152–157.
Ingbar, D. H., Hepler, K., Dowin, R., Jacobsen, E., Dunitz, J. M., Nici, L., and Jamieson, J. D. (1995) gamma-Glutamyl transpeptidase is a polarized alveolar epithelial membrane protein. Am. J. Physiol. 269, L261–L271.
Coursin, D. B., Cihla, H. P., Sempf, J., Oberley, T. D., and Oberley, L. W. (1996) An immunohistochemical analysis of antioxidant and glutathione S-transferase enzyme levels in normal and neoplastic human lung. Histol. Histopathol. 11, 851–860.
Oberley, L. W. and Oberley, T. D. (1997) Role of antioxidant enzymes in the cancer phenotype. In: Oxygen, Gene Expression, and Cellular Function. Clerch, L. B. and Massano, D. J., eds. Lung Biology in Health and Disease. 105, Marcel Dekker, Inc., New York, 279–307.
Cobbs, C. S., Levi, D. S., Aldape, K., and Israel, M. A. (1996) Manganese superoxide dismutase expression in human central nervous system tumors. Cancer Res. 56, 3192–3195.
Janssen, A. M., Bosman, C. B., Sier, C. F., Griffioen, G., Kubben, F. J., Lamers, C. B., et al. (1998) Superoxide dismutases in relation to the overall survival of colorectal cancer patients. Br. J. Cancer 78, 1051–1057.
Kahlos, K., Anttila, S., Asikainen, T., Kinnula, K., Raivio, K. O., Mattson, K., et al. (1998) Manganese superoxide dismutase in healthy human pleural mesothelium and in malignant pleural mesothelioma. Am. J. Respir. Cell Mol. Biol. 18, 570–580.
Cole, S. P., Downes, H. F., Mirski, S. E., and Clements, D. J. (1990) Alterations in glutathione and glutathione-related enzymes in a multidrug-resistant small cell lung cancer cell line. Mol. Pharmacol. 37, 192–197.
Zaman, G. J., Lankelma, J., van Tellingen, O., Beijnen, J., Dekker, H., Paulusma, C., et al. (1995) Role of glutathione in the export of compounds from cells by the multidrug-resistance-associated protein. Proc. Natl. Acad. Sci. USA 92, 7690–7694.
Rahman, I. and MacNee, W. (2000) Oxidative stress and regulation of glutathione in lung inflammation. Eur. Respir. J. 16(3), 534–554.
Iida, T., Mori, E., Mori, K., Goto, S., Urata, Y., Oka, M., Kohno, S., and Kondo, T. (1999) Co-expression of gamma-glutamylcysteine synthetase sub-units in response to cisplatin and doxorubicin in human cancer cells. Int. J. Cancer 82, 405–411.
Oguri, T., Fujiwara, Y., Isobe, T., Katoh, O., Watanabe, H., and Yamakido, M. (1998) Expression of γ-glutamylcysteine synthetase (γGCS) and multidrug resistance-associated protein (MRP), but not human canalicular multispecific organic anion transporter (cMOAT), genes correlates with exposure of human lung cancers to platinum drugs. Br. J. Cancer 77, 1089–1096.
Hatcher, E. L., Alexander, J. M., and Kang, Y. J. (1997) Decreased sensitivity to adriamycin in cadmium-resistant human lung carcinoma A549 cells. Biochem. Pharmacol. 53, 747–754.
al-Kabban, M., Stewart, M. J., Watson, I. D., and Reglinski, J. (1990) The effect of doxorubicin on the glutathione content and viability of cultured human lung cancer cell lines A549 and GLC4 210. Clin. Chim. Acta. 194, 121–129.
Jarvinen, K., Pietarinen-Runtti, P., Linnainmaa, K., Raivio, K. O., Krejsa, C. M., Kavanagh, T., and Kinnula, V. L. (2000) Antioxidant defense mechanisms of human mesothelioma and lung adenocarcinoma cells. Am. J. Physiol. Lung Cell Mol. Physiol. 278, L696–L702.
Buckley, B. J., Kent, R. S., and Whorton, A. R. (1991) Regulation of endothelial cell prostaglandin synthesis by glutathione. J. Biol. Chem. 266, 16659–16666.
Yan, T., Jiang, X., Zhang, H. J., Li, S., and Oberley, L. W. (1998) Use of commercial antibodies for detection of the primary antioxidant enzymes. Free Radic. Biol. Med. 25(6), 688–693.
Ray, S., Misso, N. L., Lenzo, J. C., Robinson, C., and Thompson, P. J. (1999) Gamma-glutamylcysteine synthetase activity in human lung epithelial (A549) cells: factors influencing its measurement. Free Radic. Biol. Med. 27, 1346–1356.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2003 Humana Press Inc., Totowa, NJ
About this protocol
Cite this protocol
Järvinen, K., Soini, Y., Kinnula, V.L. (2003). γ-Glutamylcysteine Synthetase in Lung Cancer. In: Driscoll, B. (eds) Lung Cancer. Methods in Molecular Medicine™, vol 74. Humana Press, Totowa, NJ. https://doi.org/10.1385/1-59259-323-2:211
Download citation
DOI: https://doi.org/10.1385/1-59259-323-2:211
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-0-89603-985-8
Online ISBN: 978-1-59259-323-1
eBook Packages: Springer Protocols