Interactions between cell surface protein disulphide isomerase and S-nitrosoglutathione during nitric oxide delivery

Shah, Chirag; Bell, Susannah E.; Locke, Ian C.; Chowdrey, Hardial S.; Gordge, Michael P.

doi:10.1016/j.niox.2006.08.001

Cited by 37 publications

(29 citation statements)

References 39 publications

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“…NO produced by endothelium acts on platelets to maintain them in a resting state. Exposure to NO results in a decreased number of free thiols on megakaryocyte and platelet surfaces 31 and S-nitrosylation of multiple platelet receptors including a IIb b 3 is observed following exposure to NO. 32 PDI undergoes S-nitrosylation following exposure to NO donors.…”

Section: S-nitrosylation Of Thiol Isomerasesmentioning

confidence: 99%

“…Delivery of NO from an S-NO donor into cytosol is inhibited following knockdown of PDI in HEL cells. 13 Inhibition of PDI blocks the delivery of NO from the physiologic NO donor, S-nitrosoglutathione, into both megakaryocytes 31 and into platelets. 35 PDI-mediated transnitrosylation is proposed to occur via the delivery of NO into cell membranes in the form of N 2 O 3 .…”

Section: S-nitrosylation Of Thiol Isomerasesmentioning

confidence: 99%

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Vascular thiol isomerases

Flaumenhaft

Furie

2016

Blood

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Thiol isomerases are multifunctional enzymes that influence protein structure via their oxidoreductase, isomerase, and chaperone activities. These enzymes localize at high concentrations in the endoplasmic reticulum of all eukaryotic cells where they serve an essential function in folding nascent proteins. However, thiol isomerases can escape endoplasmic retention and be secreted and localized on plasma membranes. Several thiol isomerases including protein disulfide isomerase, ERp57, and ERp5 are secreted by and localize to the membranes of platelets and endothelial cells. These vascular thiol isomerases are released following vessel injury and participate in thrombus formation. Although most of the activities of vascular thiol isomerases that contribute to thrombus formation are yet to be defined at the molecular level, allosteric disulfide bonds that are modified by thiol isomerases have been described in substrates such as αIIbβ3, αvβ3, GPIbα, tissue factor, and thrombospondin. Vascular thiol isomerases also act as redox sensors. They respond to the local redox environment and influence S-nitrosylation of surface proteins on platelets and endothelial cells. Despite our rudimentary understanding of the mechanisms by which thiol isomerases control vascular function, the clinical utility of targeting them in thrombotic disorders is already being explored in clinical trials.

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Section: S-nitrosylation Of Thiol Isomerasesmentioning

confidence: 99%

Section: S-nitrosylation Of Thiol Isomerasesmentioning

confidence: 99%

Vascular thiol isomerases

Flaumenhaft

Furie

2016

Blood

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“…The published scheme shows plausibly how a single enzyme turnover brings about NO release, but the mechanism of active site thiol regeneration, required to continue RSNO signalling, is not yet defined. Several studies have documented thiol oxidation within csPDI and loss of enzyme activity as a result of the interaction with RSNO (Zai et al, 1999;Root et al, 2004;Shah et al, 2007). Redox regeneration of csPDI may derive from both internal sources, via transmembrane oxidoreductases such as NAD(P)H oxidase, and/or from reducing equivalents present in blood plasma.…”

Section: Cell Surface Protein Disulphide Isomerase Promotes No Delivementioning

confidence: 99%

S‐nitrosothiols as selective antithrombotic agents – possible mechanisms

Gordge¹,

Xiao²

2010

British J Pharmacology

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S-nitrosothiols have a number of potential clinical applications, among which their use as antithrombotic agents has been emphasized. This is largely because of their well-documented platelet inhibitory effects, which show a degree of platelet selectivity, although the mechanism of this remains undefined. Recent progress in understanding how nitric oxide (NO)-related signalling is delivered into cells from stable S-nitrosothiol compounds has revealed a variety of pathways, in particular denitrosation by enzymes located at the cell surface, and transport of intact S-nitrosocysteine via the amino acid transporter system-L (L-AT). Differences in the role of these pathways in platelets and vascular cells may in part explain the reported platelet-selective action. In addition, emerging evidence that S-nitrosothiols regulate key targets on the exofacial surfaces of cells involved in the thrombotic process (for example, protein disulphide isomerase, integrins and tissue factor) suggests novel antithrombotic actions, which may not even require transmembrane delivery of NO.

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“…Recently it has been shown that most cells (including neurons) contain GSNO reductase activity (Jensen et al 1998;Shah et al 2007), one of the more interesting being protein disulfide isomerase (PDI) activity (Sliskovic et al 2005). Thus, neurons are likely to self-limit the levels of intracellular GSNO produced by exogenous NO administration, producing an apparent ''ceiling'' Next, neurons were perfused with 1 lM spermine NONOate for 5 min.…”

Section: Discussionmentioning

confidence: 99%

Release of intracellular Zn2+ in cultured neurons after brief exposure to low concentrations of exogenous nitric oxide

et al. 2007

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Several studies have shown intracellular Zn(2+) release and concomitant cell death after prolonged exposure to exogenous NO. In the present study, we investigated whether cortical neurons briefly exposured to exogenous NO would demonstrate similar levels of intracellular Zn(2+) release and subsequent cell death. Cortical neurons were loaded with the Zn(2+) selective fluorophore FluoZin-3 and treated with various concentrations of the NO generator, spermine NONOate. Fluorescence microscopy was used to detect and quantify intracellular Zn(2+) levels. Concomitant EDTA perfusion was used to eliminate potential effects of extracellular Zn(2+). Neurons were perfused with the heavy metal chelator TPEN to selectively eliminate Zn(2+) induced fluorescence changes. A significant increase of intracellular fluorescence was detected during a 5 min perfusion with spermine NONOate. The increase in intracellular Zn(2+) release appeared to peak at 1 microM spermine NONOate (123.8 +/- 28.5%, increase above control n = 20, P < 0.001). Further increases in spermine NONOate levels as high as 1 mM failed to further increase detectable intracellular Zn(2+) levels. The NO scavenger hemoglobin blocked the effects of spermine NONOate and the inactive analog of the spermine NONOate, spermine, was without effect. No evidence of cell death induced by any of the brief treatments with exogenous NO was observed; only prolonged incubation with much larger amounts of exogenous NO resulted in significant cell death. These data suggest that in vivo release of NO may cause elevations of intracellular Zn(2+) in cortical neurons. The possibility that release of intracellular Zn(2+) in response to NO could play a role in intracellular signaling is discussed.

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Interactions between cell surface protein disulphide isomerase and S-nitrosoglutathione during nitric oxide delivery

Cited by 37 publications

References 39 publications

Vascular thiol isomerases

Vascular thiol isomerases

S‐nitrosothiols as selective antithrombotic agents – possible mechanisms

Release of intracellular Zn2+ in cultured neurons after brief exposure to low concentrations of exogenous nitric oxide

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