title: Reductive stress linked to small HSPs, G6PD, and Nrf2 pathways in heart disease.
abstract: CONCLUSIONS
  Aerobic organisms must exist between the dueling biological metabolic processes for energy and respiration and the obligatory generation of reactive oxygen species (ROS) whose deleterious consequences can reduce survival. Wide fluctuations in harmful ROS generation are circumvented by endogenous countermeasures (i.e., enzymatic and nonenzymatic antioxidants systems) whose capacity decline with aging and are enhanced by disease states.
  
  
  BACKGROUND
  Substantial efforts on the cellular and molecular underpinnings of oxidative stress has been complemented recently by the discovery that reductive stress similarly predisposes to inheritable cardiomyopathy, firmly establishing that the biological extremes of the redox spectrum play essential roles in disease pathogenesis.
  
  
  RESULTS
  Because antioxidants by nutritional or pharmacological supplement to prevent or mitigate disease states have been largely disappointing, we hypothesize that lack of efficacy of antioxidants might be related to adverse outcomes in responders at the reductive end of the redox spectrum. As emerging concepts, such as reductive, as opposed, oxidative stress are further explored, there is an urgent and critical gap for biochemical phenotyping to guide the targeted clinical applications of therapeutic interventions.
  
  
  CONCLUSIONS
  New approaches are vitally needed for characterizing redox states with the long-term goal to noninvasively assess distinct clinical states (e.g., presymptomatic, end-stage) with the diagnostic accuracy to guide personalized medicine.
authors.affiliation: Cardiovascular Division, British Heart Foundation Centre of Research Excellence, King's College, London, UK.
authors.forename: Alison C
authors.initials: AC
authors.lastname: Brewer
authors.forename: Soumyajit Banerjee
authors.initials: SB
authors.lastname: Mustafi
authors.forename: Thomas V A
authors.initials: TV
authors.lastname: Murray
authors.forename: Namakkal Soorappan
authors.initials: NS
authors.lastname: Rajasekaran
authors.forename: Ivor J
authors.initials: IJ
authors.lastname: Benjamin
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D002374:Catalase / Q000378:metabolism; D004195:Disease Models, Animal; D042241:Early Diagnosis; D005954:Glucosephosphate Dehydrogenase / Q000502:physiology*; D005978:Glutathione / Q000378:metabolism; D006331:Heart Diseases / Q000175:diagnosis / Q000378:metabolism* / Q000628:therapy; D006360:Heat-Shock Proteins / Q000235:genetics / Q000502:physiology*; D006801:Humans; D051379:Mice; D008955:Models, Cardiovascular; D018832:Molecular Chaperones; D051267:NF-E2-Related Factor 2 / Q000502:physiology*; D009363:Neoplasm Proteins / Q000235:genetics / Q000502:physiology; D010544:Peroxidases / Q000378:metabolism; D057285:Precision Medicine; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D011993:Recombinant Fusion Proteins / Q000502:physiology; D013482:Superoxide Dismutase / Q000378:metabolism; D013879:Thioredoxins / Q000378:metabolism; D038203:alpha-Crystallin B Chain / Q000235:genetics / Q000502:physiology
chemical_list: D000975:Antioxidants; C525420:Cryab protein, mouse; D006360:Heat-Shock Proteins; C486113:Hsbp1 protein, mouse; D018832:Molecular Chaperones; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D009363:Neoplasm Proteins; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D011993:Recombinant Fusion Proteins; D038203:alpha-Crystallin B Chain; D013879:Thioredoxins; D005954:Glucosephosphate Dehydrogenase; D010544:Peroxidases; D002374:Catalase; D013482:Superoxide Dismutase; D005978:Glutathione; D000111:Acetylcysteine