Nitric Oxide Storage and Transport in Cells Are Mediated by Glutathione S-Transferase P1-1 and Multidrug Resistance Protein 1 via Dinitrosyl Iron Complexes

Lok, Hiu Chuen; Rahmanto, Yohan Suryo; Hawkins, Clare L.; Kalinowski, Danuta S.; Morrow, Charles S.; Townsend, Alan J.; Ponka, Prem; Richardson, Des R.

doi:10.1074/jbc.m111.310987

Cited by 52 publications

(113 citation statements)

References 37 publications

Supporting

Mentioning

105

Contrasting

Order By: Relevance

“…Given the short half-life of uncomplexed NO, and the need for it to be exported to carry out its extracellular functions, mechanisms for NO storage and transport are critical. Thus, Richardson and colleagues (101) have proposed that cells can form dinitrosyl-diglutathionyl-iron ((GS) 2 -Fe-(NO) 2 ) complexes as long-lived NO intermediates and have provided genetic and pharmacological evidence that these complexes can be effluxed from cells by MRP1 (Fig. 2).…”

Section: Gsh and Mrp1-mediated Transportmentioning

confidence: 99%

Multidrug Resistance Protein 1 (MRP1, ABCC1), a “Multitasking” ATP-binding Cassette (ABC) Transporter

Cole

2014

Journal of Biological Chemistry

292

245

View full text Add to dashboard Cite

The multidrug resistance protein 1 (MRP1) encoded by ABCC1 was originally discovered as a cause of multidrug resistance in tumor cells. However, it is now clear that MRP1 serves a broader role than simply mediating the ATP-dependent efflux of drugs from cells. The antioxidant GSH and the pro-inflammatory cysteinyl leukotriene C 4 have been identified as key physiological organic anions effluxed by MRP1, and an ever growing body of evidence indicates that additional lipid-derived mediators are also substrates of this transporter. As such, MRP1 is a multitasking transporter that likely influences the etiology and progression of a host of human diseases.

show abstract

Section: Gsh and Mrp1-mediated Transportmentioning

confidence: 99%

Multidrug Resistance Protein 1 (MRP1, ABCC1), a “Multitasking” ATP-binding Cassette (ABC) Transporter

Cole

2014

Journal of Biological Chemistry

292

245

View full text Add to dashboard Cite

show abstract

“…More recent studies have shown that NO generated by several different sources, including transfection with iNOS or exposure to two exogenous NO generators (i.e. GSNO or spermine NONOate), leads to iron release from wild-type murine embryonic fibroblasts, but not from murine embryonic fibroblasts from MRP1 knockout mice (37).…”

Section: Ubiquitous Gsh Transporter Mrp1 Mediates Nomediated Iron Andmentioning

confidence: 99%

“…GSH completes the coordination sphere of the NO-iron complex to form a DNIC. DNICs can be bound by GST P1-1 or effluxed out of cells via MRP1 (37,38).…”

Section: Model Of D-glucose-dependent No-mediated Iron Mobilizationmentioning

confidence: 99%

“…NDRG1 is a cytosolic protein (34,35) that is strongly up-regulated by cellular iron depletion via hypoxia-inducible factor-1␣-dependent and -independent pathways (34 -36). The effect of NO on the up-regulation of NDRG1 probably occurs through its ability to deplete the LIP with the subsequent mobilization of iron (28,(37)(38)(39). The importance of this iron pool in NO activity has been confirmed by studies showing that it provides iron for dinitrosyl-dithioliron complex (DNIC) generation (40).…”

Section: Effect Of No On Cellular Iron Metabolismmentioning

confidence: 99%

See 1 more Smart Citation

Nitrogen Monoxide (NO) Storage and Transport by Dinitrosyl-Dithiol-Iron Complexes: Long-lived NO That Is Trafficked by Interacting Proteins

Rahmanto

Kalinowski

Lane

et al. 2012

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

“…GSTP has been found to regulate the activities of a number of biologic pathways, such as c-Jun N-terminal kinase (JNK) and tumor necrosis factor receptor-associated factor 2 (Adler et al, 1999;Wu et al, 2006). Furthermore, evidence suggests that GSTP may catalyze the binding of glutathione to cellular proteins (Sglutathionylation) (Townsend et al, 2009) and facilitate the transport of nitric oxide via dinitrosyl-dithiol-iron complexes (Lok et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Altered ProteinS-Glutathionylation Identifies a Potential Mechanism of Resistance to Acetaminophen-Induced Hepatotoxicity

McGarry

Chakravarty

Wolf

et al. 2015

J Pharmacol Exp Ther

View full text Add to dashboard Cite

Acetaminophen (APAP) is the most commonly used over-thecounter analgesic. However, hepatotoxicity induced by APAP is a major clinical issue, and the factors that define sensitivity to APAP remain unclear. We have previously demonstrated that mice nulled for glutathione S-transferase Pi (GSTP) are resistant to APAP-induced hepatotoxicity. This study aims to exploit this difference to delineate pathways of importance in APAP toxicity. We used mice nulled for GSTP and heme oxygenase-1 oxidative stress reporter mice, together with a novel nanoflow liquid chromatography-tandem mass spectrometry methodology to investigate the role of oxidative stress, cell signaling, and protein S-glutathionylation in APAP hepatotoxicity. We provide evidence that the sensitivity difference between wild-type and Gstp1/2 2/2 mice is unrelated to the ability of APAP to induce oxidative stress, despite observing significant increases in c-Jun N-terminal kinase and extracellular signal-regulated kinase phosphorylation in wildtype mice. The major difference in response to APAP was in the levels of protein S-glutathionylation: Gstp1/2 2/2 mice exhibited a significant increase in the number of S-glutathionylated proteins compared with wild-type animals. Remarkably, these S-glutathionylated proteins are involved in oxidative phosphorylation, respiratory complexes, drug metabolism, and mitochondrial apoptosis. Furthermore, we found that S-glutathionylation of the rate-limiting glutathione-synthesizing enzyme, glutamate cysteine ligase, was markedly increased in Gstp1/2 2/2 mice in response to APAP. The data demonstrate that S-glutathionylation provides an adaptive response to APAP and, as a consequence, suggest that this is an important determinant in APAP hepatotoxicity. This work identifies potential novel avenues associated with cell survival for the treatment of chemical-induced hepatotoxicity.

show abstract

Nitric Oxide Storage and Transport in Cells Are Mediated by Glutathione S-Transferase P1-1 and Multidrug Resistance Protein 1 via Dinitrosyl Iron Complexes

Cited by 52 publications

References 37 publications

Multidrug Resistance Protein 1 (MRP1, ABCC1), a “Multitasking” ATP-binding Cassette (ABC) Transporter

Multidrug Resistance Protein 1 (MRP1, ABCC1), a “Multitasking” ATP-binding Cassette (ABC) Transporter

Nitrogen Monoxide (NO) Storage and Transport by Dinitrosyl-Dithiol-Iron Complexes: Long-lived NO That Is Trafficked by Interacting Proteins

Altered ProteinS-Glutathionylation Identifies a Potential Mechanism of Resistance to Acetaminophen-Induced Hepatotoxicity

Contact Info

Product

Resources

About