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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board Member: Buchner, Johannes / Ludwig, Stephan / Sies, Helmut / Turk, Boris / Wittinghofer, Alfred

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Glutathione dysregulation and the etiology and progression of human diseases

Nazzareno Ballatori1 / Suzanne M. Krance2 / Sylvia Notenboom3 / Shujie Shi4 / Kim Tieu5 / Christine L. Hammond6

1Department of Environmental Medicine, University of Rochester School of Medicine, Rochester, NY 14642, USA

2Department of Environmental Medicine, University of Rochester School of Medicine, Rochester, NY 14642, USA

3Department of Environmental Medicine, University of Rochester School of Medicine, Rochester, NY 14642, USA

4Department of Environmental Medicine, University of Rochester School of Medicine, Rochester, NY 14642, USA

5Department of Environmental Medicine, University of Rochester School of Medicine, Rochester, NY 14642, USA

6Department of Environmental Medicine, University of Rochester School of Medicine, Rochester, NY 14642, USA

Corresponding author

Citation Information: Biological Chemistry. Volume 390, Issue 3, Pages 191–214, ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: 10.1515/BC.2009.033, January 2009

Publication History

Received:
2008-10-22
Accepted:
2008-12-12
Published Online:
2009-01-23

Abstract

Glutathione (GSH) plays an important role in a multitude of cellular processes, including cell differentiation, proliferation, and apoptosis, and as a result, disturbances in GSH homeostasis are implicated in the etiology and/or progression of a number of human diseases, including cancer, diseases of aging, cystic fibrosis, and cardiovascular, inflammatory, immune, metabolic, and neurodegenerative diseases. Owing to the pleiotropic effects of GSH on cell functions, it has been quite difficult to define the role of GSH in the onset and/or the expression of human diseases, although significant progress is being made. GSH levels, turnover rates, and/or oxidation state can be compromised by inherited or acquired defects in the enzymes, transporters, signaling molecules, or transcription factors that are involved in its homeostasis, or from exposure to reactive chemicals or metabolic intermediates. GSH deficiency or a decrease in the GSH/glutathione disulfide ratio manifests itself largely through an increased susceptibility to oxidative stress, and the resulting damage is thought to be involved in diseases, such as cancer, Parkinson's disease, and Alzheimer's disease. In addition, imbalances in GSH levels affect immune system function, and are thought to play a role in the aging process. Just as low intracellular GSH levels decrease cellular antioxidant capacity, elevated GSH levels generally increase antioxidant capacity and resistance to oxidative stress, and this is observed in many cancer cells. The higher GSH levels in some tumor cells are also typically associated with higher levels of GSH-related enzymes and transporters. Although neither the mechanism nor the implications of these changes are well defined, the high GSH content makes cancer cells chemoresistant, which is a major factor that limits drug treatment. The present report highlights and integrates the growing connections between imbalances in GSH homeostasis and a multitude of human diseases.

Keywords: aging; cancer; cardiovascular diseases; glutathione; metabolic diseases; neurodegenerative diseases

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