title: Nitrogen monoxide (NO) storage and transport by dinitrosyl-dithiol-iron complexes: long-lived NO that is trafficked by interacting proteins.
abstract: Nitrogen monoxide (NO) markedly affects intracellular iron metabolism, and recent studies have shown that molecules traditionally involved in drug resistance, namely GST and MRP1 (multidrug resistance-associated protein 1), are critical molecular players in this process. This is mediated by interaction of these proteins with dinitrosyl-dithiol-iron complexes (Watts, R. N., Hawkins, C., Ponka, P., and Richardson, D. R. (2006) Proc. Natl. Acad. Sci. U.S.A. 103, 7670-7675; Lok, H. C., Suryo Rahmanto, Y., Hawkins, C. L., Kalinowski, D. S., Morrow, C. S., Townsend, A. J., Ponka, P., and Richardson, D. R. (2012) J. Biol. Chem. 287, 607-618). These complexes are bioavailable, have a markedly longer half-life compared with free NO, and form in cells after an interaction between iron, NO, and glutathione. The generation of dinitrosyl-dithiol-iron complexes acts as a common currency for NO transport and storage by MRP1 and GST P1-1, respectively. Understanding the biological trafficking mechanisms involved in the metabolism of NO is vital for elucidating its many roles in cellular signaling and cytotoxicity and for development of new therapeutic targets.
authors.affiliation: Department of Pathology, University of Sydney, Sydney, New South Wales 2006, Australia.
authors.forename: Yohan
authors.initials: Y
authors.lastname: Suryo Rahmanto
authors.forename: Danuta S
authors.initials: DS
authors.lastname: Kalinowski
authors.forename: Darius J R
authors.initials: DJ
authors.lastname: Lane
authors.forename: Hiu Chuen
authors.initials: HC
authors.lastname: Lok
authors.forename: Vera
authors.initials: V
authors.lastname: Richardson
authors.forename: Des R
authors.initials: DR
authors.lastname: Richardson
mesh_terms: D000818:Animals; D001693:Biological Transport, Active / Q000502:physiology; D005978:Glutathione / Q000378:metabolism; D051549:Glutathione S-Transferase pi / Q000378:metabolism*; D006801:Humans; D058085:Iron Compounds / Q000378:metabolism*; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D009589:Nitrogen Oxides / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D005978:Glutathione; D051549:Glutathione S-Transferase pi; D058085:Iron Compounds; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009569:Nitric Oxide; D009589:Nitrogen Oxides; C420456:dinitrosyl iron thiosulfate; C496556:GSTP1 protein, human; C421109:multidrug resistance-associated protein 1