title: Oxidative stress, redox regulation and diseases of cellular differentiation.
abstract: BACKGROUND
  Within cells, there is a narrow concentration threshold that governs whether reactive oxygen species (ROS) induce toxicity or act as second messengers.
  
  
  METHODS
  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.
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, 70 President St., DD410, Charleston, SC 29425, USA.
authors.forename: Zhi-Wei
authors.initials: ZW
authors.lastname: Ye
authors.affiliation: Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, 70 President St., DD410, Charleston, SC 29425, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutical and Biomedical Sciences, Medical University of South Carolina, 274 Calhoun Street MSC 141, Charleston, SC 29425-1410, USA.
authors.forename: Danyelle M
authors.initials: DM
authors.lastname: Townsend
authors.affiliation: Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, 70 President St., DD410, Charleston, SC 29425, USA. Electronic address: tewk@musc.edu.
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Tew
mesh_terms: D000111:Acetylcysteine / Q000627:therapeutic use; D002454:Cell Differentiation / Q000502:physiology*; D016166:Free Radical Scavengers / Q000627:therapeutic use; D006801:Humans; D008954:Models, Biological; D009765:Obesity / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
chemical_list: D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D000111:Acetylcysteine
keywords: Diseases of cellular differentiation; Glutathione; Glutathione S-transferase; Reactive oxygen species; Redox; Redox active drugs