Glutathione dysregulation and the etiology and progression of human diseases. Biol Chem

Department of Environmental Medicine, University of Rochester School of Medicine, Rochester, NY 14642, USA.
Biological Chemistry (Impact Factor: 2.69). 02/2009; 390(3):191-214. DOI: 10.1515/BC.2009.033
Source: PubMed

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.

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Available from: Shujie Shi, Jun 12, 2014
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    • "Then, in order to assess the cellular antioxidant capacity, we determined the glutathione redox status. The ratio between oxidized and reduced glutathione serves as an important indicator for oxidative stress evaluation in cells and tissues (Ballatori et al., 2009). In this study, we observed a significant increase in GSSG/ GSH ratio in exposed population (p < 0.05; Table 1, Fig. 2F), result in agreement with several previous studies (Diouf et al., 2006; Liu et al., 2009). "
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    Environmental Pollution 07/2015; 206:247-255. DOI:10.1016/j.envpol.2015.06.032 · 3.90 Impact Factor
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    • "All rights reserved catalyzed by c-glutamylcysteine synthetase (Gsh1) and glutathione synthetase (Gsh2), is the most abundant intracellular low molecular weight thiol within cells. It may have an outstanding function because it is involved in several physiological processes such as the control of intracellular redox status by reacting with ROS or binding to sulfhydryl groups on proteins (glutathiolation), drug metabolism, DNA synthesis, protein stabilization, mitochondrial function and integrity, cell proliferation, and apoptosis (Grant et al., 1996; Ballatori et al., 2009; Pallard o et al., 2009). GSH is also a substrate for enzymes such as glutathione transferases, which catalyze the nucleophilic attack on several electrophilic xenobiotics favoring the efflux of conjugates from cells (Hayes et al., 2005). "
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    • "This finding is compatible with the reported enhancement of cellular antioxidant defences due to low H 2 O 2 concentrations (Chen et al., 2005) and with the increase in GSH levels after mild oxidative stress (Weber et al., 2007). GSH plays a pivotal role in regulating cellular thiol-redox status, protecting against oxidants and electrophiles, and in conjugating and eliminating toxicants (Ballatori et al., 2009). Our results show that BSO, the specific inhibitor of GSH biosynthesis, does not prevent the adaptive response showing that the observed increase in GSH levels is not responsible for the α-TOS primed PC3 cell response. "
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