Redox balance in Cystic Fibrosis

• Type of Material: Article
• Authors: Assem Ziady, Emory University; Jason Hansen, Emory University
• Language: English
• Date: 2014-07-01
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2014 Elsevier Ltd.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.biocel.2014.03.006
• Title of Journal or Parent Work: International Journal of Biochemistry and Cell Biology
• ISSN: 1357-2725
• Volume: 52
• Start Page: 113
• End Page: 123
• Grant/Funding Information: This work was funded by the NHLBI (1R01HL109362-01 (Ziady) and the Cystic Fibrosis Foundation.
• Keywords: GLUTATHIONE TRANSPORT; SELENIUM DEFICIENCY; TRANSMEMBRANE CONDUCTANCE; Oxidative stress; Nrf2 dysfunction; Biochemistry & Molecular Biology; PSEUDOMONAS-AERUGINOSA; CFTR; OXYGEN-CONSUMPTION; Antioxidants; Life Sciences & Biomedicine; REDUCED GLUTATHIONE; Science & Technology; NF-KAPPA-B; Cell Biology; PROTEOMIC ANALYSIS; OXIDATIVE STRESS; EPITHELIAL-CELLS
• Research Categories: Chemistry, Biochemistry; Biology, Cell

Abstract

The homeostatic balance between oxidants and antioxidants in biological systems is known as redox balance, and is regulated by complex processes. Redox balance regulates many of the known cellular pathways and disease processes. The dysregulation of redox balance can lead to acute or long-term oxidative or reductive stresses that are associated with many of the abnormalities observed in cystic fibrosis (CF). Over the past 5 decades researchers have examined contributors to redox dysregulation, their molecular products, and their impact on ion transport, cell proliferation, inflammation, bacterial killing, and the metabolism of nucleic acids, proteins, and lipids in CF. CF patients exhibit elevated markers of oxidative stress when compared to non-CF healthy controls; however, whether the reported redox imbalance is sufficient to produce pathology has been controversial. In addition, comparisons between CF and non-CF disease controls have been lacking. To better understand the mechanisms which mediate the generation of oxidants and antioxidants in CF and the importance of their balance in effecting oxidative or reductive stress, we will review the determinants of redox balance in the blood, lumen, and cellular compartments. From the perspective of methodological application, we will focus on the approaches most often used to study oxidant and antioxidants in CF, including biochemical, proteomic, metabolomic, and lipidomic studies, with a discussion of the few transcriptomic analyses that predict changes in the expression of regulators of redox. Finally, we will discuss the utility of oxidants and antioxidants as biomarkers of disease and the use of antioxidant therapy in CF. This article is part of a Directed Issue entitled: Cystic Fibrosis: From o-mics to cell biology, physiology, and therapeutic advances.