title: Glutathione during embryonic development.
abstract: BACKGROUND
  Glutathione (GSH) is a ubiquitous, non-protein biothiol in cells. It plays a variety of roles in detoxification, redox regulation and cellular signaling. Many processes that can be regulated through GSH are critical to developing systems and include cellular proliferation, differentiation and apoptosis. Understanding how GSH functions in these aspects can provide insight into how GSH regulates development and how during periods of GSH imbalance how these processes are perturbed to cause malformation, behavioral deficits or embryonic death.
  
  
  METHODS
  Here, we review the GSH system as it relates to events critical for normal embryonic development and differentiation.
  
  
  CONCLUSIONS
  This review demonstrates the roles of GSH extend beyond its role as an antioxidant but rather GSH acts as a mediator of numerous processes through its ability to undergo reversible oxidation with cysteine residues in various protein targets. Shifts in GSH redox potential cause an increase in S-glutathionylation of proteins to change their activity. As such, redox potential shifts can act to modify protein function on a possible longer term basis. A broad group of targets such as kinases, phosphatases and transcription factors, all critical to developmental signaling, is discussed.
  
  
  CONCLUSIONS
  Glutathione regulation of redox-sensitive events is an overlying theme during embryonic development and cellular differentiation. Various stresses can change GSH redox states, we strive to determine developmental stages of redox sensitivity where insults may have the most impactful damaging effect. In turn, this will allow for better therapeutic interventions and preservation of normal developmental signaling. This article is part of a Special Issue entitled Redox regulation of differentiation and de-differentiation.
authors.affiliation: Department of Physiology and Developmental Biology, College of Life Sciences, Brigham Young University, Provo, UT 84602, United States. Electronic address: jason_hansen@byu.edu.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Hansen
authors.affiliation: Department of Environmental Health Sciences, School of Public Health, University of Michigan, Ann Arbor, MI 40109-2029, United States.
authors.forename: Craig
authors.initials: C
authors.lastname: Harris
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D049109:Cell Proliferation; D047108:Embryonic Development / Q000502:physiology*; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D010084:Oxidation-Reduction; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D014157:Transcription Factors; D005978:Glutathione
keywords: Cysteine; Development; Differentiation; Embryo; Glutathione; Redox potential