title: Hydrogen peroxide sensing and signaling by protein kinases in the cardiovascular system.
abstract: CONCLUSIONS
  Oxidants were once principally considered perpetrators of injury and disease. However, this has become an antiquated view, with cumulative evidence showing that the oxidant hydrogen peroxide serves as a signaling molecule. Hydrogen peroxide carries vital information about the redox state of the cell and is crucial for homeostatic regulation during health and adaptation to stress.
  
  
  BACKGROUND
  In this review, we examine the contemporary concepts for how hydrogen peroxide is sensed and transduced into a biological response by introducing post-translational oxidative modifications on select proteins. Oxidant sensing and signaling by kinases are of particular importance as they integrate oxidant signals into phospho-regulated pathways. We focus on CAMKII, PKA, and PKG, kinases whose redox regulation has notable impact on cardiovascular function.
  
  
  RESULTS
  In addition, we examine the mechanism for regulating intracellular hydrogen peroxide, considering the net concentrations that may accumulate. The effects of endogenously generated oxidants are often modeled by applying exogenous hydrogen peroxide to cells or tissues. Here we consider whether model systems exposed to exogenous hydrogen peroxide have relevance to systems where the oxidant is generated endogenously, and if so, what concentration can be justified in terms of relevance to health and disease.
  
  
  CONCLUSIONS
  Improving our understanding of hydrogen peroxide signaling and the sensor proteins that it can modify will help us develop new strategies to regulate intracellular signaling to prevent disease.
authors.affiliation: Department of Cardiology, King's College London, The Rayne Institute, St. Thomas' Hospital, London, UK.
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Burgoyne
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Oka
authors.forename: Niloofar
authors.initials: N
authors.lastname: Ale-Agha
authors.forename: Philip
authors.initials: P
authors.lastname: Eaton
mesh_terms: D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000502:physiology*; D002319:Cardiovascular System / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology*; D017869:Cyclic GMP-Dependent Protein Kinases / Q000502:physiology*; D003545:Cysteine / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism* / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology; D008715:Methionine / Q000378:metabolism; D008955:Models, Cardiovascular; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000378:metabolism; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D015290:Second Messenger Systems / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D013481:Superoxides / Q000378:metabolism
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C000606290:SOD1 protein, human; D013438:Sulfhydryl Compounds; D013481:Superoxides; D008715:Methionine; D006861:Hydrogen Peroxide; D010088:Oxidoreductases; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D017868:Cyclic AMP-Dependent Protein Kinases; D017869:Cyclic GMP-Dependent Protein Kinases; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D003545:Cysteine