title: Blood removal therapy in hereditary hemochromatosis induces a stress response resulting in improved genome integrity.
abstract: Hereditary hemochromatosis (HH) is a common disease of iron metabolism, manifesting with iron overload and affecting up to 1% of individuals of northern European descent. Untreated HH can result in irreversible damage of the liver and pancreas, potentially leading to cancer and diabetes. Therapy consists of normalizing iron stores by repeated blood donations (phlebotomy). Treated HH patients have normal survival rates and report less tiredness after phlebotomy; however, it is not understood why musculoskeletal symptoms may persist in spite of iron removal. We hypothesize that phlebotomy therapy does not simply reverse iron accumulation but has additional effects at the subcellular level. In particular, the systemic impact of phlebotomy on mitochondria and genome integrity is largely unknown.
  
  
  
  The effects of phlebotomy therapy on mitochondrial iron proteins and genome integrity were investigated in peripheral blood mononuclear blood cells from HH patients.
  
  
  
  After the reduction of systemic iron load in these patients with phlebotomy, we observed increased expression of mitochondrial superoxide dismutase, reduced iron sulfur assembly protein (Iscu1/2), and improved genome integrity.
  
  
  
  We conclude that phlebotomy therapy in HH does not merely restore systemic iron homeostasis, but induces an "oxidative stress" defense response that manifests as improved genome integrity. These findings provide novel insights into an ancient therapy.
authors.affiliation: Department of Medical Biochemistry, Oslo University Hospital.
authors.forename: Sonia
authors.initials: S
authors.lastname: Distante
authors.affiliation: Department of Medical Biochemistry, Oslo University Hospital.
authors.forename: Joakim
authors.initials: J
authors.lastname: Eikeland
authors.affiliation: Department of Medical Biochemistry, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Tina
authors.initials: T
authors.lastname: Pawar
authors.affiliation: Department of Medical Biochemistry, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Ragnhild
authors.initials: R
authors.lastname: Skinnes
authors.affiliation: Department of Medical Biochemistry, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Kari
authors.initials: K
authors.lastname: Høie
authors.affiliation: Department of Medical Biochemistry, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Panpan
authors.initials: P
authors.lastname: You
authors.affiliation: Department of Medical Biochemistry, Oslo University Hospital.|Department of Medical Biochemistry, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Lars
authors.initials: L
authors.lastname: Mørkrid
authors.affiliation: Department of Medical Biochemistry, Oslo University Hospital.|Department of Medical Biochemistry, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Lars
authors.initials: L
authors.lastname: Eide
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D042822:Genomic Instability; D006432:Hemochromatosis / Q000628:therapy*; D006801:Humans; D019190:Iron Overload / Q000628:therapy; D033862:Iron-Binding Proteins; D007506:Iron-Sulfur Proteins / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000378:metabolism*; D018384:Oxidative Stress; D018962:Phlebotomy / Q000009:adverse effects*; D013482:Superoxide Dismutase / Q000378:metabolism; D055815:Young Adult
chemical_list: C506160:ISCU protein, human; D033862:Iron-Binding Proteins; D007506:Iron-Sulfur Proteins; D024101:Mitochondrial Proteins; D013482:Superoxide Dismutase