title: Ferritin heavy chain mediates the protective effect of heme oxygenase-1 against oxidative stress.
abstract: The phenomenon that heme oxygenase-1 (HO-1) protects cell from injury yet its enzymatic product, iron, may facilitate generation of free radical has been long puzzling. Here we establish a functional connection between ferritin heavy chain (FHC) and HO-1. In human lupus nephritis HO-1 and FHC are colocalized within the glomeruli. In rodent anti-Thy1 (thymocyte antigen 1) induced glomerulonephritis, heme oxygenase blockade lowers the expression of FHC and accelerates mesangial cell death. Stimulation of heme oxygenase in cultured rat mesangial cell enhances its resistance to hydrogen peroxide, whereas FHC knockdown by RNA interference compromises this salutary effect. RNA interference of HO-1 makes the cell more susceptible to hydrogen peroxide, which can be rescued by forced expression of wild-type FHC but not mutants that lose the capacity of iron storage and ferroxidase activity. Phosphorylation of JunD was not sustained in these cells. Microarray analysis identifies four candidate transcriptional factors that may regulate the HO-1-induced transcription of FHC. Our results support the role of FHC in neutralizing the iron toxicity as well as mediating the protective effect of HO-1 in response to oxidative stress.
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital Hsin-Chu Branch, Hsin Chu City 30059, Taiwan; Research Center for Developmental Biology and Regenerative Medicine, National Taiwan University, Taipei, Taiwan. Electronic address: hcheng@wustl.edu.
authors.forename: Hui-Teng
authors.initials: HT
authors.lastname: Cheng
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei 10002, Taiwan; Department of Geriatrics and Gerontology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei 10002, Taiwan.
authors.forename: Chung-Jen
authors.initials: CJ
authors.lastname: Yen
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei 10002, Taiwan.
authors.forename: Chen-Chih
authors.initials: CC
authors.lastname: Chang
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei 10002, Taiwan; Institute of Toxicology, College of Medicine, National Taiwan University, Taipei 10002, Taiwan.
authors.forename: Kuo-Tong
authors.initials: KT
authors.lastname: Huang
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei 10002, Taiwan.
authors.forename: Kuo-Hsuan
authors.initials: KH
authors.lastname: Chen
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital Hsin-Chu Branch, Hsin Chu City 30059, Taiwan.
authors.forename: Rui-Yang
authors.initials: RY
authors.lastname: Zhang
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei 10002, Taiwan.
authors.forename: Ping-Yi
authors.initials: PY
authors.lastname: Lee
authors.affiliation: Graduate Institute of Immunology, College of Medicine, National Taiwan University, Taipei 10002, Taiwan.
authors.forename: Shi-Chuen
authors.initials: SC
authors.lastname: Miaw
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei 10002, Taiwan. Electronic address: 007378@ntuh.gov.tw.
authors.forename: Jenq-Wen
authors.initials: JW
authors.lastname: Huang
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei 10002, Taiwan; Institute of Toxicology, College of Medicine, National Taiwan University, Taipei 10002, Taiwan; Department of Integrated Diagnostics and Therapeutics, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei 10002, Taiwan. Electronic address: ckchiang@ntuh.gov.tw.
authors.forename: Chih-Kang
authors.initials: CK
authors.lastname: Chiang
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei 10002, Taiwan.
authors.forename: Kwan-Dun
authors.initials: KD
authors.lastname: Wu
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei 10002, Taiwan.
authors.forename: Kuan-Yu
authors.initials: KY
authors.lastname: Hung
mesh_terms: D000818:Animals; D001052:Apoferritins / Q000502:physiology*; D005920:Glomerular Mesangium / Q000166:cytology / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000502:physiology*; D018384:Oxidative Stress; D051381:Rats
chemical_list: D001052:Apoferritins; D051547:Heme Oxygenase-1
keywords: Ferritin heavy chain; Heme oxygenase-1; Inflammation; Oxidative stress