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Interaction between RSNO and H2S: The formation, stability, and NO-donating capacity of SSNO- and the effect of SSNO- on platelet activation

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abstract
H2S is a gaseous mediator that has its own beneficial effects on vascular physiology. It has been implicated in the modulation of cellular processes including vessel tone/constriction, blood pressure, and tissue reperfusion. When S-nitrosothiols (RSNOs) react with excess H2S, they form several intermediates including the soluble guanylate cyclase (sGC) activating nitrosopersulfide (SSNO-). However, the stability and reactivity of this intermediate remained under debate, and hence, the relevance of nitric oxide (NO) and HS- reactions had not been established. With novel and confirmatory data, my work has demonstrated the capacity of SSNO- to donate NO and the mechanism by which it does so. I have shown that SSNO- has a half-life in anaerobic and aqueous conditions of 40 minutes. I employed UV/visible spectroscopy, electron paramagnetic resonance (EPR), and took advantage of the redox reactivity of liganded hemoglobin under aerobic and anaerobic conditions, to determine that SSNO- spontaneously releases very little NO upon decomposition. Using the selectivity of ferricatalase, I have also shown that nitroxyl (HNO) release from SSNO- decomposition is unlikely. However, I have determined that NO is acquired from SSNO- in the presence of vacant heme. Indeed, our data shows that a vacant heme is necessary to acquire NO from SSNO-, which indicates a direct heme-SSNO- reaction. SSNO- reacts with ferrous and ferri-hemes, but more efficiently with ferrihemoglobin (metHb). I have further demonstrated the stability of SSNO- in platelet-rich plasma, in which, the inhibition of platelet activation in platelets treated with SSNO- is comparable to those treated with S-nitrosoglutathione (GSNO).
subject
Hydrogen sulfide
nitric oxide
nitrosopersulfide
nitrosothiol
nitroxyl
contributor
Bolden, Crystal Antoinette (author)
Kim-Shapiro, Daniel (committee chair)
Furdui, Cristina (committee member)
Vachharajani, Vidula (committee member)
King, S. Bruce (committee member)
date
2017-06-15T08:36:02Z (accessioned)
2019-06-14T08:30:14Z (available)
2017 (issued)
degree
Molecular Medicine and Translational Science (discipline)
embargo
2019-06-14 (terms)
identifier
http://hdl.handle.net/10339/82212 (uri)
language
en (iso)
publisher
Wake Forest University
title
Interaction between RSNO and H2S: The formation, stability, and NO-donating capacity of SSNO- and the effect of SSNO- on platelet activation
type
Dissertation

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