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

doi:10.1016/j.bbagen.2017.02.021

Review

. 2017 May;1861(5 Pt A):995-999.

doi: 10.1016/j.bbagen.2017.02.021. Epub 2017 Feb 17.

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

Z Kovacevic¹, S Sahni², H Lok², M J Davies³, D A Wink⁴, D R Richardson⁵

Affiliations

¹ Molecular Pharmacology and Pathology Program, Department of Pathology, University of Sydney, Sydney, New South Wales 2006, Australia. Electronic address: z.kovacevic@sydney.edu.au.
² Molecular Pharmacology and Pathology Program, Department of Pathology, University of Sydney, Sydney, New South Wales 2006, Australia.
³ Department of Biomedical Sciences, Building 12.6, Panum Institute, University of Copenhagen, Blegdamsvej 3, Copenhagen 2200,Denmark.
⁴ Cancer Inflammation Program, National Cancer Institute, National Institutes of Health, Frederick, MD, USA.
⁵ 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.

PMID: 28219722
DOI: 10.1016/j.bbagen.2017.02.021

Review

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 et al. Biochim Biophys Acta Gen Subj. 2017 May.

. 2017 May;1861(5 Pt A):995-999.

doi: 10.1016/j.bbagen.2017.02.021. Epub 2017 Feb 17.

Authors

Z Kovacevic¹, S Sahni², H Lok², M J Davies³, D A Wink⁴, D R Richardson⁵

Affiliations

¹ Molecular Pharmacology and Pathology Program, Department of Pathology, University of Sydney, Sydney, New South Wales 2006, Australia. Electronic address: z.kovacevic@sydney.edu.au.
² Molecular Pharmacology and Pathology Program, Department of Pathology, University of Sydney, Sydney, New South Wales 2006, Australia.
³ Department of Biomedical Sciences, Building 12.6, Panum Institute, University of Copenhagen, Blegdamsvej 3, Copenhagen 2200,Denmark.
⁴ Cancer Inflammation Program, National Cancer Institute, National Institutes of Health, Frederick, MD, USA.
⁵ 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.

PMID: 28219722
DOI: 10.1016/j.bbagen.2017.02.021

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.

Keywords: MRP1; Macrophages; Nitric oxide.

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

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

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