Regulation and control of nitric oxide (NO) in macrophages: Protecting the "professional killer cell" from its own cytotoxic arsenal via MRP1 and GSTP1.

Z Kovacevic, S Sahni, H Lok, M J Davies, D A Wink, D R Richardson

Journal: Biochimica et biophysica acta. General subjects 2017;1861(5 Pt A):995-999

PMID: 28219722

Full Text on Elsevier Science View on PubMed

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.

Address: Molecular Pharmacology and Pathology Program, Department of Pathology, University of Sydney, Sydney, New South Wales 2006, Australia. Electronic address: [email protected].; Molecular Pharmacology and Pathology Program, Department of Pathology, University of Sydney, Sydney, New South Wales 2006, Australia.; Department of Biomedical Sciences, Building 12.6, Panum Institute, University of Copenhagen, Blegdamsvej 3, Copenhagen 2200,Denmark.; Cancer Inflammation Program, National Cancer Institute, National Institutes of Health, Frederick, MD, USA.; Molecular Pharmacology and Pathology Program, Department of Pathology, University of Sydney, Sydney, New South Wales 2006, Australia. Electronic address: [email protected].

DOI: 10.1016/j.bbagen.2017.02.021

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MeSH Terms: Glutathione, Glutathione S-Transferase pi, Humans, Killer Cells, Natural, Macrophages, Multidrug Resistance-Associated Proteins, Nitric Oxide, Protective Agents