Nitrogen Monoxide (NO) and Glucose

Watts, Ralph; Richardson, Des R.

doi:10.1074/jbc.m006318200

Cited by 46 publications

(32 citation statements)

References 63 publications

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“…We investigated NO-mediated 59 Fe release from cells and found it to be energy-and temperature-dependent (16,17). We also reported that glucose metabolism by the hexose monophosphate shunt (HMPS) stimulated NO-mediated Fe efflux from cells (16,17).…”

Section: Nitrogen Monoxide (No)-mediated Iron Release From Cells Is Lmentioning

confidence: 99%

“…We also reported that glucose metabolism by the hexose monophosphate shunt (HMPS) stimulated NO-mediated Fe efflux from cells (16,17). Moreover, using the GSH synthesis inhibitor L-buthionine-[S,R]-sulfoximine (BSO), we showed that a product of the HMPS, namely GSH, was essential for NO-mediated Fe release (16)(17)(18). We proposed that NO-mediated Fe efflux occurred as a GSFe-NO complex, which is exported from cells by energy-dependent transport (17).…”

Section: Nitrogen Monoxide (No)-mediated Iron Release From Cells Is Lmentioning

confidence: 99%

“…We previously showed cellular 59 Fe release with a range of NO donors, e.g., SperNO, S-nitroso-N-acetylpenicillamine, and Snitrosoglutathione, but not with their precursors that do not contain NO•, namely spermine, N-acetylpenicillamine, or GSH, respectively (10,16,17). These agents also did not affect cell viability (10,16,17).…”

Section: No-mediated Fe Efflux Is Greater In Mrp1-hyperexpressing Cellsmentioning

confidence: 99%

“…Previously, we showed the GSH synthesis inhibitor BSO prevented NO-mediated 59 Fe release from a variety of cells (16)(17)(18). Further, BSO is known to effectively prevent GSH-dependent MRP1 transport (19,23).…”

Section: No-mediated Fe Efflux Is Greater In Mrp1-hyperexpressing Cellsmentioning

confidence: 99%

“…1A we compare MCF7-WT and MCF7-VP cells to the well characterized NO-mediated Fe release from LMTK Ϫ and SK-N-MC cells (10,(16)(17)(18). Cells were prelabeled with the physiological Fe donor 59 Fe-transferrin ( 59 Fe-Tf; 0.75 M) for 3 h at 37°C before being subjected to a Fe efflux assay (Fig.…”

Section: No-mediated Fe Efflux Is Greater In Mrp1-hyperexpressing Cellsmentioning

confidence: 99%

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Nitrogen monoxide (NO)-mediated iron release from cells is linked to NO-induced glutathione efflux via multidrug resistance-associated protein 1

Watts

Hawkins

Ponka

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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116

119

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Nitrogen monoxide (NO) plays a role in the cytotoxic mechanisms of activated macrophages against tumor cells by inducing iron (Fe) release. We have shown that NO-mediated Fe efflux from cells required glutathione (GSH), and we have hypothesized that a GS–Fe–NO complex was released. Hence, we studied the role of the GSH-conjugate transporter multidrug resistance-associated protein 1 (MRP1) in NO-mediated Fe efflux. MCF7-VP cells overexpressing MRP1 exhibited a 3- to 4-fold increase in NO-mediated 59 Fe and GSH efflux compared with WT cells (MCF7-WT) over 4 h. Similar results were found for other MRP1-overexpressing cell types but not those expressing another drug efflux pump, P-glycoprotein. NO-mediated 59 Fe and GSH efflux were temperature- and energy-dependent and were significantly decreased by the GSH-depleting agent and MRP1 transport inhibitor l -buthionine-[ S , R ]-sulfoximine. Other MRP1 inhibitors, MK571, probenecid, and difloxacin, significantly inhibited NO-mediated 59 Fe release. EPR spectroscopy demonstrated the dinitrosyl-dithiol-Fe complex (DNIC) peak in NO-treated cells was increased by MRP1 inhibitors, indicating inhibited DNIC transport from cells. The extent of DNIC accumulation correlated with the ability of MRP1 inhibitors to prevent NO-mediated 59 Fe efflux. MCF7-VP cells were more sensitive than MCF7-WT cells to growth inhibition by effects of NO, which was potentiated by l -buthionine-[ S , R ]-sulfoximine. These data indicate the importance of GSH in NO-mediated inhibition of proliferation. Collectively, NO stimulates Fe and GSH efflux from cells via MRP1. Active transport of NO by MRP1 overcomes diffusion that is inefficient and nontargeted, which has broad ramifications for understanding NO biology.

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Section: Nitrogen Monoxide (No)-mediated Iron Release From Cells Is Lmentioning

confidence: 99%

Section: Nitrogen Monoxide (No)-mediated Iron Release From Cells Is Lmentioning

confidence: 99%

Section: No-mediated Fe Efflux Is Greater In Mrp1-hyperexpressing Cellsmentioning

confidence: 99%

Section: No-mediated Fe Efflux Is Greater In Mrp1-hyperexpressing Cellsmentioning

confidence: 99%

Section: No-mediated Fe Efflux Is Greater In Mrp1-hyperexpressing Cellsmentioning

confidence: 99%

See 3 more Smart Citations

Nitrogen monoxide (NO)-mediated iron release from cells is linked to NO-induced glutathione efflux via multidrug resistance-associated protein 1

Watts

Hawkins

Ponka

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

116

119

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Electric field assisted multicomponent reaction in a microfluidic reactor for superior conversion and yield

et al. 2018

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We explore the improvements in yield and conversion of a chemical reaction inside a two‐phase microfluidic reactor when subjected to an externally applied alternating current (AC) electric field. A computational fluid dynamic (CFD) framework has been developed to incorporate the descriptions of the two‐phase flow, multicomponent transport and reaction, and the Maxwell's stresses generated at oil‐water interface owing to the presence of the externally applied electric field. The CFD model ensures that the reactants are flown into a microchannel together with the oil and water phases before the reaction takes place at the interface and products diffuse back to the bulk phases. The study unveils that the variation in the intensity of the AC field helps in converting a two‐phase stratified flow into an oil‐in‐water microemulsion composed of oil slugs, plugs, or droplets. Importantly, the results also suggest that harnessing the vortices inside or outside these flow patterns helps in the improvement in mass transfer across the interface, which can be employed to improve the yield and conversion of a reaction. We have shown an example case of a pseudo‐first order reaction for which the variation in frequency and intensity of AC field is found to form higher surface‐to‐volume‐ratio flow patterns having a higher throughput. The convective recirculation in and around these miniaturized flow morphologies increase the rate of mass transfer, mixing of reactant and products, conversion of reactant, and yield of products. The results reported can be of significance in the design and development of future advanced‐flow rector technologies.

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Iron‐sulfur glutaredoxin 2 protects oligodendrocytes against damage induced by nitric oxide release from activated microglia

Lepka

Volbracht

Bill

et al. 2017

Glia

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Demyelinated brain lesions, a hallmark of autoimmune neuroinflammatory diseases like multiple sclerosis, result from oligodendroglial cell damage. Activated microglia are considered a major source of nitric oxide and subsequent peroxynitrite-mediated damage of myelin. Here, we provide biochemical and biophysical evidence that the oxidoreductase glutaredoxin 2 inhibits peroxynitrite formation by transforming nitric oxide into dinitrosyl-diglutathionyl-iron-complexes. Glutaredoxin 2 levels influence both survival rates of primary oligodendrocyte progenitor cells and preservation of myelin structure in cerebellar organotypic slice cultures challenged with activated microglia or nitric oxide donors. Of note, glutaredoxin 2-mediated protection is not linked to its enzymatic activity as oxidoreductase, but to the disassembly of its uniquely coordinated iron-sulfur cluster using glutathione as non-protein ligand. The protective effect of glutaredoxin 2 is connected to decreased protein carbonylation and nitration. In line, brain lesions of mice suffering from experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis, show decreased glutaredoxin 2 expression and increased nitrotyrosine formation indicating that this type of protection is missing in the inflamed central nervous system. Our findings link inorganic biochemistry to neuroinflammation and identify glutaredoxin 2 as a protective factor against neuroinflammation-mediated myelin damage. Thus, improved availability of glutathione-coordinated iron-sulfur clusters emerges as a potential therapeutic approach in inflammatory demyelination.

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Nitrogen Monoxide (NO) and Glucose

Cited by 46 publications

References 63 publications

Nitrogen monoxide (NO)-mediated iron release from cells is linked to NO-induced glutathione efflux via multidrug resistance-associated protein 1

Nitrogen monoxide (NO)-mediated iron release from cells is linked to NO-induced glutathione efflux via multidrug resistance-associated protein 1

Electric field assisted multicomponent reaction in a microfluidic reactor for superior conversion and yield

Iron‐sulfur glutaredoxin 2 protects oligodendrocytes against damage induced by nitric oxide release from activated microglia

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