title: Thrombopoietin Protects Cardiomyocytes from Iron-Overload Induced Oxidative Stress and Mitochondrial Injury.
abstract: OBJECTIVE
  Thalassaemia accompanied with iron-overload is common in Hong Kong. Iron-overload induced cardiomyopathy is the commonest cause of morbidity and mortality in patients with β-thalassaemia. Chronic iron-overload due to blood transfusion can cause cardiac failure. Decreased antioxidant defence and increased ROS production may lead to oxidative stress and cell injury. Iron-overload may lead to heart tissue damage through lipid peroxidation in response to oxidative stress, and a great diversity of toxic aldehydes are formed when lipid hydroperoxides break down in heart and plasma.
  
  
  METHODS
  Iron entry into embryonic heart H9C2 cells was determined by calcein assay using a fluorometer. Reactive oxygen species (ROS) production in cells treated with FeCl3 or thrombopoietin (TPO) was monitored by using the fluorescent probe H2DCFDA. Changes in mitochondrial membrane potential of H9C2 cells were quantified by using flow cytometry.
  
  
  RESULTS
  We demonstrated that iron induced oxidative stress and apoptosis in cardiomyocytes, and that iron increased ROS production and reduced cell viability in a dose-dependent manner. Iron treatment increased the proportion of cells with JC-1 monomers, indicating a trend of drop in the mitochondrial membrane potential. TPO exerted a cardio-protective effect on iron-induced apoptosis.
  
  
  CONCLUSIONS
  These findings suggest that iron-overload leads to the generation of ROS and further induces apoptosis in cardiomyocytes via mitochondrial pathways. TPO might exert a protective effect on iron-overload induced apoptosis via inhibiting oxidative stress and suppressing the mitochondrial pathways in cardiomyocytes.
authors.affiliation: Department of Pediatrics, Nanfang Hospital, Southern Medical University, Guangzhou, PR China.
authors.forename: Shing
authors.initials: S
authors.lastname: Chan
authors.forename: Godfrey Chifung
authors.initials: GC
authors.lastname: Chan
authors.forename: Jieyu
authors.initials: J
authors.lastname: Ye
authors.forename: Qizhou
authors.initials: Q
authors.lastname: Lian
authors.forename: Jianliang
authors.initials: J
authors.lastname: Chen
authors.forename: Mo
authors.initials: M
authors.lastname: Yang
mesh_terms: D002460:Cell Line; D006801:Humans; D019190:Iron Overload / Q000378:metabolism*; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects*; D018384:Oxidative Stress; D013926:Thrombopoietin / Q000494:pharmacology*
chemical_list: D013926:Thrombopoietin