Journal
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
Volume 1850, Issue 8, Pages 1607-1621Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbagen.2014.11.010
Keywords
Diseases of cellular differentiation; Glutathione; Glutathione S-transferase; Reactive oxygen species; Redox; Redox active drugs
Categories
Funding
- National Institutes of Health [CA08660, CA117259]
- South Carolina SmartState program
- National Institutes of Health from Extramural Research Facilities Program of National Center for Research Resources [C06 RR015455]
- Drug Metabolism and Clinical Pharmacology shared Resource, Hollings Cancer Center, Medical University of South Carolina
- Swedish Research Council [524-2011-6998]
- National Institutes of Health (NCRR - COBRE in Oxidants, Redox Balance and Stress Signaling) [P20RR024485]
- NATIONAL CANCER INSTITUTE [R01CA085660, R41CA117259] Funding Source: NIH RePORTER
- NATIONAL CENTER FOR RESEARCH RESOURCES [C06RR015455, P20RR024485] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [P20GM103542] Funding Source: NIH RePORTER
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Background: Within cells, there is a narrow concentration threshold that governs whether reactive oxygen species (ROS) induce toxicity or act as second messengers. Scope of review: We discuss current understanding of how ROS arise, facilitate cell signaling, cause toxicities and disease related to abnormal cell differentiation and those (primarily) sulfur based pathways that provide nucleophilicity to offset these effects. Primaly conclusions: Cellular redox homeostasis mediates a plethora of cellular pathways that determine life and death events. For example, ROS intersect with GSH based enzyme pathways to influence cell differentiation, a process integral to normal hematopoiesis, but also affecting a number of diverse cell differentiation related human diseases. Recent attempts to manage such pathologies have focused on intervening in some of these pathways, with the consequence that differentiation therapy targeting redox homeostasis has provided a platform for drug discovery and development. General Significance: The balance between electrophilic oxidative stress and protective biomolecular nucleophiles predisposes the evolution of modern life forms. Imbalances of the two can produce aberrant redox homeostasis with resultant pathologies. Understanding the pathways involved provides opportunities to consider interventional strategies. This article is part of a Special Issue entitled Redox regulation of differentiation and de-differentiation. (C) 2014 Elsevier B.V. All rights reserved.
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