The mechanism of nitrogen monoxide (NO)-mediated iron mobilization from cells. NO intercepts iron before incorporation into ferritin and indirectly mobilizes iron from ferritin in a glutathione-dependent manner.

作者： Ralph N. Watts , Des R. Richardson

DOI: 10.1046/J.1432-1033.2002.02987.X

关键词: Pentose phosphate pathway 、 Glutathione 、 Biophysics 、 Nitric oxide 、 Cytotoxic T cell 、 Transferrin 、 Cell 、 Ferritin 、 Biochemistry 、 DNA synthesis 、 Chemistry

摘要: Nitrogen monoxide (NO) is a cytotoxic effector molecule produced by macrophages that results in Fe mobilization from tumour target cells which inhibits DNA synthesis and mitochondrial respiration. It well known NO has high affinity for Fe, we showed NO-mediated markedly potentiated glutathione (GSH) generated the hexose monophosphate shunt [Watts, R.N. & Richardson, D.R. (2001) J. Biol. Chem. 276, 4724–4732]. We hypothesized GSH completes coordination shell of an NO–Fe complex released cell. In this report have extended our studies to further characterize mechanism mobilization. Native PAGE 59Fe-autoradiography shows decreased ferritin-59Fe levels prelabelled with [59Fe]transferrin. cells, increased 3.5−fold when were reincubated control media between 30 240 min. contrast, NO, 10-fold compared after 240-min reincubation. However, could not remove ferritin cell lysates. Our data suggest intercepts 59Fe on route ferritin, indirectly facilitates removal protein. Studies using GSH-depleting agent, l-buthionine-(S,R)-sulphoximine, indicated reduction via was GSH-dependent. Competition experiments permeable chelators demonstrated both bind similar pool. requires cellular metabolism order effect does occur passive diffusion down concentration gradient. Based results, propose model glucose-dependent

参考文章(54)

DR Richardson, K Milnes, None, The Potential of Iron Chelators of the Pyridoxal Isonicotinoyl Hydrazone Class as Effective Antiproliferative Agents II: The Mechanism of Action of Ligands Derived From Salicylaldehyde Benzoyl Hydrazone and 2-Hydroxy-1-Naphthylaldehyde Benzoyl Hydrazone Blood. ,vol. 89, pp. 3025- 3038 ,(1997) , 10.1182/BLOOD.V89.8.3025

G. Weiss, B. Goossen, W. Doppler, D. Fuchs, K. Pantopoulos, G. Werner-Felmayer, H. Wachter, M.W. Hentze, Translational regulation via iron-responsive elements by the nitric oxide/NO-synthase pathway The EMBO Journal. ,vol. 12, pp. 3651- 3657 ,(1993) , 10.1002/J.1460-2075.1993.TB06039.X

A Jacobs, Low molecular weight intracellular iron transport compounds. Blood. ,vol. 50, pp. 433- 439 ,(1977) , 10.1182/BLOOD.V50.3.433.433

Frederick P Nestel, Robert N Greene, Krikor Kichian, Premysl Ponka, Wayne S Lapp, None, Activation of macrophage cytostatic effector mechanisms during acute graft-versus-host disease : release of intracellular iron and nitric oxide-mediated cytostasis Blood. ,vol. 96, pp. 1836- 1843 ,(2000) , 10.1182/BLOOD.V96.5.1836.H8001836_1836_1843

Andrew J. Lipton, Michael A. Johnson, Timothy Macdonald, Michael W. Lieberman, David Gozal, Benjamin Gaston, S -Nitrosothiols signal the ventilatory response to hypoxia Nature. ,vol. 413, pp. 171- 174 ,(2001) , 10.1038/35093117

DR Richardson, EH Tran, P Ponka, None, The potential of iron chelators of the pyridoxal isonicotinoyl hydrazone class as effective antiproliferative agents. Blood. ,vol. 86, pp. 4295- 4306 ,(1995) , 10.1182/BLOOD.V86.11.4295.BLOODJOURNAL86114295

J.C. Drapier, C. Pellat, Y. Henry, Generation of EPR-detectable nitrosyl-iron complexes in tumor target cells cocultured with activated macrophages. Journal of Biological Chemistry. ,vol. 266, pp. 10162- 10167 ,(1991) , 10.1016/S0021-9258(18)99204-5

Des R Richardson, Prem Ponka, Daniel Vyoral, None, Distribution of Iron in Reticulocytes After Inhibition of Heme Synthesis With Succinylacetone: Examination of the Intermediates Involved in Iron Metabolism Blood. ,vol. 87, pp. 3477- 3488 ,(1996) , 10.1182/BLOOD.V87.8.3477.BLOODJOURNAL8783477

O.W. Griffith, A. Meister, Potent and specific inhibition of glutathione synthesis by buthionine sulfoximine (S-n-butyl homocysteine sulfoximine). Journal of Biological Chemistry. ,vol. 254, pp. 7558- 7560 ,(1979) , 10.1016/S0021-9258(18)35980-5

10.

N.R. Bastian, C.Y. Yim, J.B. Hibbs, W.E. Samlowski, Induction of iron-derived EPR signals in murine cancers by nitric oxide. Evidence for multiple intracellular targets. Journal of Biological Chemistry. ,vol. 269, pp. 5127- 5131 ,(1994) , 10.1016/S0021-9258(17)37664-0

The mechanism of nitrogen monoxide (NO)-mediated iron mobilization from cells. NO intercepts iron before incorporation into ferritin and indirectly mobilizes iron from ferritin in a glutathione-dependent manner.

来源期刊

我的账户

The mechanism of nitrogen monoxide (NO)-mediated iron mobilization from cells. NO intercepts iron before incorporation into ferritin and indirectly mobilizes iron from ferritin in a glutathione-dependent manner.

来源期刊

相似文章 10

我的账户