Haem oxygenase-1 prevents cell death by regulating cellular iron.
Haem oxygenase-1 (HO1) is a heat-shock protein that is induced by stressful stimuli. Here we demonstrate a cytoprotective role for HO1: cell death produced by serum deprivation, staurosporine or etoposide is markedly accentuated in cells from mice with a targeted deletion of the HO1 gene, and greatly reduced in cells that overexpress HO1. Iron efflux from cells is augmented by HO1 transfection and reduced in HO1-deficient fibroblasts. Iron accumulation in HO1-deficient cells explains their death: iron chelators protect HO1-deficient fibroblasts from cell death. Thus, cytoprotection by HO1 is attributable to its augmentation of iron efflux, reflecting a role for HO1 in modulating intracellular iron levels and regulating cell viability.
Ferris
C D
CD
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. cferris@jhmi.edu
Jaffrey
S R
SR
Sawa
A
A
Takahashi
M
M
Brady
S D
SD
Barrow
R K
RK
Tysoe
S A
SA
Wolosker
H
H
Barañano
D E
DE
Doré
S
S
Poss
K D
KD
Snyder
S H
SH
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003001:Cloning, Molecular; D016895:Culture Media, Serum-Free; D005047:Etoposide / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D017353:Gene Deletion; D006419:Heme Oxygenase (Decyclizing) / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D051547:Heme Oxygenase-1; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008565:Membrane Proteins; D051379:Mice; D018345:Mice, Knockout; D011994:Recombinant Proteins / Q000378:metabolism; D012867:Skin / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D019311:Staurosporine / Q000494:pharmacology; D014162:Transfection
D016895:Culture Media, Serum-Free; D008565:Membrane Proteins; D011994:Recombinant Proteins; D005047:Etoposide; D007501:Iron; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; D019311:Staurosporine