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Proc Natl Acad Sci U S A. Mar 29, 1994; 91(7): 2607–2610.

Heme oxygenase 1 mediates an adaptive response to oxidative stress in human skin fibroblasts.


Oxidative stress of human skin fibroblasts by treatment with ultraviolet A (UVA) radiation has been shown to lead to an increase in levels of the heme catabolizing enzyme heme oxygenase 1 [heme, hydrogen-donor:oxygen oxidoreductase (alpha-methene-oxidizing, hydroxylating), EC] and the iron storage protein ferritin. Here we show that human skin fibroblasts, preirradiated with UVA, sustain less membrane damage during a subsequent exposure to UVA radiation than cells that had not been preirradiated. Pretreating cells with heme oxygenase 1 antisense oligonucleotide inhibited the irradiation-dependent induction of both the heme oxygenase I enzyme and ferritin and abolished the protective effect of preirradiation. Inhibition of the UVA preirradiation-dependent increase in ferritin, but not heme oxygenase, with desferrioxamine also abolished the protection. This identifies heme oxygenase 1 as a crucial enzymatic intermediate in an oxidant stress-inducible antioxidant defense mechanism, involving ferritin, in human skin fibroblasts.

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  • Hiwasa T, Sakiyama S. Increase in the synthesis of a Mr 32,000 protein in BALB/c 3T3 cells after treatment with tumor promoters, chemical carcinogens, metal salts, and heat shock. Cancer Res. 1986 May;46(5):2474–2481. [PubMed]
  • Caltabiano MM, Koestler TP, Poste G, Greig RG. Induction of 32- and 34-kDa stress proteins by sodium arsenite, heavy metals, and thiol-reactive agents. J Biol Chem. 1986 Oct 5;261(28):13381–13386. [PubMed]
  • Taketani S, Kohno H, Yoshinaga T, Tokunaga R. The human 32-kDa stress protein induced by exposure to arsenite and cadmium ions is heme oxygenase. FEBS Lett. 1989 Mar 13;245(1-2):173–176. [PubMed]
  • Stocker R. Induction of haem oxygenase as a defence against oxidative stress. Free Radic Res Commun. 1990;9(2):101–112. [PubMed]
  • Tomaro ML, Frydman J, Frydman RB. Heme oxygenase induction by CoCl2, Co-protoporphyrin IX, phenylhydrazine, and diamide: evidence for oxidative stress involvement. Arch Biochem Biophys. 1991 May 1;286(2):610–617. [PubMed]
  • Jornot L, Junod AF. Variable glutathione levels and expression of antioxidant enzymes in human endothelial cells. Am J Physiol. 1993 May;264(5 Pt 1):L482–L489. [PubMed]
  • Keyse SM, Tyrrell RM. Both near ultraviolet radiation and the oxidizing agent hydrogen peroxide induce a 32-kDa stress protein in normal human skin fibroblasts. J Biol Chem. 1987 Oct 25;262(30):14821–14825. [PubMed]
  • Keyse SM, Tyrrell RM. Heme oxygenase is the major 32-kDa stress protein induced in human skin fibroblasts by UVA radiation, hydrogen peroxide, and sodium arsenite. Proc Natl Acad Sci U S A. 1989 Jan;86(1):99–103. [PMC free article] [PubMed]
  • Applegate LA, Luscher P, Tyrrell RM. Induction of heme oxygenase: a general response to oxidant stress in cultured mammalian cells. Cancer Res. 1991 Feb 1;51(3):974–978. [PubMed]
  • Vile GF, Tyrrell RM. Oxidative stress resulting from ultraviolet A irradiation of human skin fibroblasts leads to a heme oxygenase-dependent increase in ferritin. J Biol Chem. 1993 Jul 15;268(20):14678–14681. [PubMed]
  • Nath KA, Balla G, Vercellotti GM, Balla J, Jacob HS, Levitt MD, Rosenberg ME. Induction of heme oxygenase is a rapid, protective response in rhabdomyolysis in the rat. J Clin Invest. 1992 Jul;90(1):267–270. [PMC free article] [PubMed]
  • Balla G, Jacob HS, Balla J, Rosenberg M, Nath K, Apple F, Eaton JW, Vercellotti GM. Ferritin: a cytoprotective antioxidant strategem of endothelium. J Biol Chem. 1992 Sep 5;267(25):18148–18153. [PubMed]
  • Tyrrell RM, Pidoux M. Quantitative differences in host cell reactivation of ultraviolet-damaged virus in human skin fibroblasts and epidermal keratinocytes cultured from the same foreskin biopsy. Cancer Res. 1986 Jun;46(6):2665–2669. [PubMed]
  • Decker T, Lohmann-Matthes ML. A quick and simple method for the quantitation of lactate dehydrogenase release in measurements of cellular cytotoxicity and tumor necrosis factor (TNF) activity. J Immunol Methods. 1988 Nov 25;115(1):61–69. [PubMed]
  • Yoshida T, Biro P, Cohen T, Müller RM, Shibahara S. Human heme oxygenase cDNA and induction of its mRNA by hemin. Eur J Biochem. 1988 Feb 1;171(3):457–461. [PubMed]
  • Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. [PubMed]
  • Radin NS. Extraction of tissue lipids with a solvent of low toxicity. Methods Enzymol. 1981;72:5–7. [PubMed]
  • Gaboriau F, Morlière P, Marquis I, Moysan A, Gèze M, Dubertret L. Membrane damage induced in cultured human skin fibroblasts by UVA irradiation. Photochem Photobiol. 1993 Oct;58(4):515–520. [PubMed]
  • Eisenstein RS, Garcia-Mayol D, Pettingell W, Munro HN. Regulation of ferritin and heme oxygenase synthesis in rat fibroblasts by different forms of iron. Proc Natl Acad Sci U S A. 1991 Feb 1;88(3):688–692. [PMC free article] [PubMed]
  • Balla G, Vercellotti GM, Muller-Eberhard U, Eaton J, Jacob HS. Exposure of endothelial cells to free heme potentiates damage mediated by granulocytes and toxic oxygen species. Lab Invest. 1991 May;64(5):648–655. [PubMed]

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