title: Coupling heme and iron metabolism via ferritin H chain.
abstract: CONCLUSIONS
  Inflammation and immunity can be associated with varying degrees of heme release from hemoproteins, eventually leading to cellular and tissue iron (Fe) overload, oxidative stress, and tissue damage. Presumably, these deleterious effects contribute to the pathogenesis of systemic infections.
  
  
  BACKGROUND
  Heme release from hemoglobin sensitizes parenchyma cells to undergo programmed cell death in response to proinflammatory cytokines, such as tumor necrosis factor. This cytotoxic effect is driven by a mechanism involving intracellular accumulation of free radicals, which sustain the activation of the c-Jun N-terminal kinase (JNK) signaling transduction pathway. While heme catabolism by heme oxygenase-1 (HO-1) prevents programmed cell death, this cytoprotective effect requires the co-expression of ferritin H (heart/heavy) chain (FTH), which controls the pro-oxidant effect of labile Fe released from the protoporphyrin IX ring of heme. This antioxidant effect of FTH restrains JNK activation, whereas JNK activation inhibits FTH expression, a cross talk that controls metabolic adaptation to cellular Fe overload associated with systemic infections.
  
  
  CONCLUSIONS
  Identification and characterization of the mechanisms via which FTH provides metabolic adaptation to tissue Fe overload should provide valuable information to our current understanding of the pathogenesis of systemic infections as well as other immune-mediated inflammatory diseases.
authors.affiliation: Inflammation Laboratory, Instituto Gulbenkian de Ciência , Oeiras, Portugal .
authors.forename: Raffaella
authors.initials: R
authors.lastname: Gozzelino
authors.forename: Miguel P
authors.initials: MP
authors.lastname: Soares
mesh_terms: D000818:Animals; D001052:Apoferritins / Q000502:physiology*; D006418:Heme / Q000378:metabolism*; D051547:Heme Oxygenase-1 / Q000502:physiology; D006706:Homeostasis; D006801:Humans; D007113:Immunity, Innate; D007501:Iron / Q000378:metabolism*
chemical_list: D006418:Heme; D001052:Apoferritins; D007501:Iron; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1