Article

Nitrogen monoxide (NO) storage and transport by dinitrosyl-dithiol-iron complexes: long-lived NO that is trafficked by interacting proteins.

Department of Pathology, University of Sydney, Sydney, New South Wales 2006, Australia.
Journal of Biological Chemistry (impact factor: 4.77). 03/2012; 287(10):6960-8. DOI:10.1074/jbc.R111.329847 pp.6960-8
Source: PubMed

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.

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Keywords

Acad
 
biological trafficking mechanisms
 
cellular signaling
 
common currency
 
critical molecular players
 
cytotoxicity
 
dinitrosyl-dithiol-iron complexes
 
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drug resistance
 
elucidating
 
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glutathione
 
intracellular iron metabolism
 
Morrow
 
multidrug resistance-associated protein 1
 
new therapeutic targets
 
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Richardson
 
Suryo Rahmanto