Glutathione dysregulation and the etiology and progression of human diseases

By N. Ballatori, Suzanne M Krance, S. Notenboom, Shujie Shi, K. Tieu, C. Hammond. Biological chemistry, 2009

1,031 citations recorded by the source corpus.

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.

Subfields: Biochemistry, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/b61a82e94ed3ab6150de9babbdc2c99442c4d3cf

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In Biochemistry

1. S. Baldelli
2. K. Aquilano
3. M. Ciriolo

In Molecular Biology

1. Shelly C. Lu
2. S. Baldelli
3. K. Aquilano
4. M. Ciriolo

Citations in the corpus

• Glutathione: new roles in redox signaling for an old antioxidant (2014, background): “On the basis of these knowledge, it is not surprising that alterations in GSH homeostasis have been implicated in the etiology and/or progression of many human diseases (Ballatori et al., 2009).”
• GLUTATHIONE SYNTHESIS (2012, background): “There is accumulating data that reduced GSH levels occur in many human diseases and they contribute to worsening of the condition [4].”
• Oxidative stress in bone remodeling: role of antioxidants. (2017, background): “Indeed, GSH is involved in osteoblast and osteoclast differentiation as well as in osteoporosis and other bone diseases (14, 17, 65).”