title: Regulation and control of nitric oxide (NO) in macrophages: Protecting the "professional killer cell" from its own cytotoxic arsenal via MRP1 and GSTP1.
abstract: We recently demonstrated that a novel storage and transport mechanism for nitric oxide (NO) mediated by glutathione-S-transferase P1 (GSTP1) and multidrug resistance protein 1 (MRP1/ABCC1), protects M1-macrophage (M1-MØ) models from large quantities of endogenous NO. This system stores and transports NO as dinitrosyl-dithiol-iron complexes (DNICs) composed of iron, NO and glutathione (GSH). Hence, this gas with contrasting anti- and pro-tumor effects, which has been assumed to be freely diffusible, is a tightly-regulated species in M1-MØs. These control systems prevent NO cytotoxicity and may be responsible for delivering cytotoxic NO as DNICs via MRP1 from M1-MØs, to tumor cell targets.
authors.affiliation: Molecular Pharmacology and Pathology Program, Department of Pathology, University of Sydney, Sydney, New South Wales 2006, Australia. Electronic address: z.kovacevic@sydney.edu.au.
authors.forename: Z
authors.initials: Z
authors.lastname: Kovacevic
authors.affiliation: Molecular Pharmacology and Pathology Program, Department of Pathology, University of Sydney, Sydney, New South Wales 2006, Australia.
authors.forename: S
authors.initials: S
authors.lastname: Sahni
authors.affiliation: Molecular Pharmacology and Pathology Program, Department of Pathology, University of Sydney, Sydney, New South Wales 2006, Australia.
authors.forename: H
authors.initials: H
authors.lastname: Lok
authors.affiliation: Department of Biomedical Sciences, Building 12.6, Panum Institute, University of Copenhagen, Blegdamsvej 3, Copenhagen 2200,Denmark.
authors.forename: M J
authors.initials: MJ
authors.lastname: Davies
authors.affiliation: Cancer Inflammation Program, National Cancer Institute, National Institutes of Health, Frederick, MD, USA.
authors.forename: D A
authors.initials: DA
authors.lastname: Wink
authors.affiliation: Molecular Pharmacology and Pathology Program, Department of Pathology, University of Sydney, Sydney, New South Wales 2006, Australia. Electronic address: d.richardson@med.usyd.edu.au.
authors.forename: D R
authors.initials: DR
authors.lastname: Richardson
mesh_terms: D005978:Glutathione / Q000378:metabolism; D051549:Glutathione S-Transferase pi / Q000378:metabolism*; D006801:Humans; D007694:Killer Cells, Natural / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D020011:Protective Agents / Q000378:metabolism*
chemical_list: D005978:Glutathione; D051549:Glutathione S-Transferase pi; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009569:Nitric Oxide; D020011:Protective Agents; C421109:multidrug resistance-associated protein 1
keywords: MRP1; Macrophages; Nitric oxide