Carbon monoxide signaling and soluble guanylyl cyclase: Facts, myths, and intriguing possibilities

Wen, Lu; Yang, Xiaoxiao; Wang, Binghe

doi:10.1016/j.bcp.2022.115041

Cited by 12 publications

(9 citation statements)

References 156 publications

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“…One view is that relatively high local concentrations of CO can still be maintained when there is little NO left to diffuse to sGC because CO is much more stable than NO. As a result, the concentration of CO is sufficient to competitively inhibit the binding of NO, while the initiated sGC activity by CO is much lower, allowing for an impactful blocking effect [ 154 ]. In addition to competing for the downstream binding sites, CO has regulatory effects on NOS and NO on HO.…”

Section: Comentioning

confidence: 99%

Local delivery of gaseous signaling molecules for orthopedic disease therapy

Sun

Wang

et al. 2023

J Nanobiotechnol

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Over the past decade, a proliferation of research has used nanoparticles to deliver gaseous signaling molecules for medical purposes. The discovery and revelation of the role of gaseous signaling molecules have been accompanied by nanoparticle therapies for their local delivery. While most of them have been applied in oncology, recent advances have demonstrated their considerable potential in diagnosing and treating orthopedic diseases. Three of the currently recognized gaseous signaling molecules, nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S), are highlighted in this review along with their distinctive biological functions and roles in orthopedic diseases. Moreover, this review summarizes the progress in therapeutic development over the past ten years with a deeper discussion of unresolved issues and potential clinical applications.

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Section: Comentioning

confidence: 99%

Local delivery of gaseous signaling molecules for orthopedic disease therapy

Sun

Wang

et al. 2023

J Nanobiotechnol

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“…CO is a well-known gaseous ligand for various hemoproteins. In vivo , at least 25 hemoproteins were observed to bind CO with K D s spanning almost 8 orders of magnitude from low nM to high μM range ( Lu et al, 2022 ). The ability for CO to activate sGC was first discovered in 1987 in a study of the anti-platelet aggregation activity of CO ( Brune and Ullrich, 1987 ).…”

Section: Introductionmentioning

confidence: 99%

“…The problem of CO-dependent regulation of sGC is further exacerbated by the high affinity for CO of the abundant cellular heme-containing globins. CO binding affinity of hemoglobin, myoglobin, neuroglobin or cytoglobin is 3–6 orders of magnitude higher than that of sGC ( Lu et al, 2022 ). Therefore in vivo , it is highly unlikely that any significant amount of sGC-CO is formed.…”

Section: Introductionmentioning

confidence: 99%

Soluble guanylyl cyclase: Molecular basis for ligand selectivity and action in vitro and in vivo

Wu¹,

Sharina

Eisenacher

2022

Front. Mol. Biosci.

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Nitric oxide (NO), carbon monoxide (CO), oxygen (O2), hydrogen sulfide (H2S) are gaseous molecules that play important roles in the physiology and pathophysiology of eukaryotes. Tissue concentrations of these physiologically relevant gases vary remarkable from nM range for NO to high μM range of O2. Various hemoproteins play a significant role in sensing and transducing cellular signals encoded by gaseous molecules or in transporting them. Soluble guanylyl cyclase (sGC) is a hemoprotein that plays vital roles in a wide range of physiological functions and combines the functions of gaseous sensor and signal transducer. sGC uniquely evolved to sense low non-toxic levels of NO and respond to elevated NO levels by increasing its catalytic ability to generate the secondary signaling messenger cyclic guanosine monophosphate (cGMP). This review discusses sGC’s gaseous ligand selectivity and the molecular basis for sGC function as high-affinity and selectivity NO receptor. The effects of other gaseous molecules and small molecules of cellular origin on sGC’s function are also discussed.

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“…11 It controls various critical cellular processes, with mitochondria being its primary target, and manifests anti-inflammatory, antiproliferative, and cytoprotective properties. [12][13] It soon gained attention as a promising therapeutic agent in several settings, such as organ transplantation or cancer treatments, [14][15][16][17][18] but its acute toxicity 19 poses severe limitations in the administration under a clinical scenario. A controlled and targeted release is, therefore, essential.…”

Section: Introductionmentioning

confidence: 99%

Proton-Coupled Triplet-Triplet Energy Transfer: Carbon Monoxide Photorelease from Porphyrin-Flavonol Hybrids

Ramundo

Janos

Muchová

et al. 2022

Preprint

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A new photochemical mechanism, termed proton-coupled energy transfer (PCEnT), was recently discovered in anthracene-phenol-pyridine triads (Pettersson Rimgard et al., Science 2022, 377, 742). It couples an electronic transition to nuclear motions allowing Förster (dipole-dipole) energy transfer even though there is no overlap of the donor emission and acceptor absorption spectra. Here, we extend this concept to triplet-triplet energy transfer (TEnT) from light-harvesting porphyrin to a covalently bound flavonol group. While direct TEnT to the flavonol acceptor would be highly endergonic, it becomes feasible thanks to the flavonol energy stabilization upon intramolecular proton transfer in the triplet state. We describe the overall mechanism as proton-coupled TEnT (PCTEnT) – a one-photon process that enables the activation of a UV-absorbing chromophore by visible light. Several porphyrin-flavonol hybrids containing 4 flavonol units attached to the porphyrin meso positions were designed as photoactivatable carbon monoxide (CO)-releasing molecules (photoCORMs). The photoreaction mechanism was studied by steady-state and transient absorption spectroscopy techniques and complementary quantum-chemical calculations. While intrinsically toxic, CO is an endogenous signaling molecule with therapeutic potential that regulates various physiological processes, and photoCORMs offer precise spatial and temporal control of CO administration. We evaluated the viability of the human hepatoblastoma HepG2 cells in the presence of the studied hybrids and tested the effects associated with the intracellular release of CO and the production of singlet oxygen. We demonstrate that the PCTEnT process could be used to devise new photoactivatable molecular devices with potential biological applications.

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Carbon monoxide signaling and soluble guanylyl cyclase: Facts, myths, and intriguing possibilities

Cited by 12 publications

References 156 publications

Local delivery of gaseous signaling molecules for orthopedic disease therapy

Local delivery of gaseous signaling molecules for orthopedic disease therapy

Soluble guanylyl cyclase: Molecular basis for ligand selectivity and action in vitro and in vivo

Proton-Coupled Triplet-Triplet Energy Transfer: Carbon Monoxide Photorelease from Porphyrin-Flavonol Hybrids

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