Redox regulation of soluble guanylyl cyclase

Shah, Rohan; Sanker, Subramaniam; Wood, Katherine C.; Durgin, Brittany G; Straub, Adam C.

doi:10.1016/j.niox.2018.03.013

Cited by 49 publications

(39 citation statements)

References 105 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…2d). In case of oxidative stress, in oxidized state of GC-1 becomes desensitized to available NO, leading to a decrease in cGMP production necessary for activation of downstream proteins and pathways 27 . As a result, preconditioning with riociguat significantly ameliorated nitro-oxidative stress in the myocardium of RioHTX animals, as evidenced by a significant decrease in nitrotyrosine immunoreactivity ( Fig.…”

Section: Discussionmentioning

confidence: 99%

Stimulation of soluble guanylate cyclase improves donor organ function in rat heart transplantation

Benke

Németh

Sayour

et al. 2020

Sci Rep

View full text Add to dashboard Cite

Heart transplantation remains the definitive therapy of end-stage heart failure. Ischemia-reperfusion injury occurring during transplantation is a primary determinant of long-term outcome of heart transplantation and primary graft insufficiency. Modification of the nitric oxide/soluble guanylate cyclase/cyclic guanosine monophosphate signaling pathway appears to be one of the most promising among the pharmacological interventional options. We aimed at characterizing the cardio-protective effects of the soluble guanylate cyclase stimulator riociguat in a rat model of heterotopic heart transplantation. Donor Lewis rats were treated orally with either riociguat or placebo for two days (n = 9) in each transplanted group and (n = 7) in donor groups. Following explantation, hearts were heterotopically transplanted. After one hour reperfusion, left ventricular pressure-volume relations and coronary blood flow were recorded. Molecular biological measurements and histological examination were also completed. Left ventricular contractility (systolic pressure: 117 ± 13 vs. 48 ± 5 mmHg, p < 0.001; dP/dt max : 2963 ± 221 vs. 1653 ± 159 mmHg/s, p < 0.001), active relaxation (dP/dt min : −2014 ± 305 vs. −1063 ± 177 mmHg/s, p = 0.02; all at 120 µl of left ventricular volume), and alteration of coronary blood flow standardized to heart weight (2.55 ± 0.32 vs. 1.67 ± 0.22 ml/min/g, p = 0.03) were markedly increased following preconditioning with riociguat. Myocardial apoptosis markers were also significantly reduced in the riociguat pretreated group as well as the antioxidant markers were elevated. Pharmacological preconditioning with riociguat decreases ischemia-reperfusion injury and improves donor organ function in our animal model of heart transplantation. Therefore, riociguat might be a potential cardioprotective agent. Heart transplantation (HTX) is still the optimal procedure for patients with end-stage heart failure, when other medical or surgical interventions have failed. The primary graft failure (PGF) remains an important problem after heart transplantation; it is reported to have an incidence up to even 40% 1. Ischemia/reperfusion (I/R) injury is a major determinant of PGF. The deleterious effects of I/R injury are mediated mainly by reactive oxygen (ROS) and nitrogen species (RNS) such as peroxynitrite 2 , production of which during ischemia is enhanced. This is followed by an extra burst of reactive species generation taking place at reperfusion. ROS and RNS tissue concentrations at any time are dependent on the balance of their production and elimination, the latter being actively regulated by antioxidant enzymes in the endogenous antioxidant system, such as superoxide dismutase (SOD) and catalase 3. Therefore, in order to reduce I/R injury, reduction of the amount of ROS and RNS either by decreasing production or enhancing elimination is essential. A feasible option to achieve this goal during transplantation is pharmacological preconditioning the heart before explantation. Oxidative and nitrosative stress-mediate...

show abstract

Section: Discussionmentioning

confidence: 99%

Stimulation of soluble guanylate cyclase improves donor organ function in rat heart transplantation

Benke

Németh

Sayour

et al. 2020

Sci Rep

View full text Add to dashboard Cite

show abstract

“…The pathophysiological relevance of oxidative stress on NO/sGC signaling and the impact on disease progression is still poorly understood. However, recently and also presented on the last cGMP meeting in 2017, it was shown that vascular SMC express a reductase (CYB5R3) turning back oxidized sGC into the native form (Shah et al 2018). More recently, it has been demonstrated that knock out of CYB5R3 in vascular SMC is linked to a hypertensive phenotype by reducing NOmediated sGC stimulation (Durgin et al 2019).…”

Section: Pgc Structure and Functionmentioning

confidence: 99%

cGMP: a unique 2nd messenger molecule – recent developments in cGMP research and development

Friebe

Sandner

Schmidtko

2019

Naunyn-Schmiedeberg's Arch Pharmacol

101

View full text Add to dashboard Cite

Cyclic guanosine monophosphate (cGMP) is a unique second messenger molecule formed in different cell types and tissues. cGMP targets a variety of downstream effector molecules and, thus, elicits a very broad variety of cellular effects. Its production is triggered by stimulation of either soluble guanylyl cyclase (sGC) or particulate guanylyl cyclase (pGC); both enzymes exist in different isoforms. cGMP-induced effects are regulated by endogenous receptor ligands such as nitric oxide (NO) and natriuretic peptides (NPs). Depending on the distribution of sGC and pGC and the formation of ligands, this pathway regulates not only the cardiovascular system but also the kidney, lung, liver, and brain function; in addition, the cGMP pathway is involved in the pathogenesis of fibrosis, inflammation, or neurodegeneration and may also play a role in infectious diseases such as malaria. Moreover, new pharmacological approaches are being developed which target sGC-and pGC-dependent pathways for the treatment of various diseases. Therefore, it is of key interest to understand this pathway from scratch, beginning with the molecular basis of cGMP generation, the structure and function of both guanylyl cyclases and cGMP downstream targets; research efforts also focus on the subsequent signaling cascades, their potential crosstalk, and also the translational and, ultimately, the clinical implications of cGMP modulation. This review tries to summarize the contributions to the "9th International cGMP Conference on cGMP Generators, Effectors and Therapeutic Implications" held in Mainz in 2019. Presented data will be discussed and extended also in light of recent landmark findings and ongoing activities in the field of preclinical and clinical cGMP research.

show abstract

“…On the other hand, apo-sGC β1 associates with Hsp90 much more strongly than sGC α1, which prevents the formation of heme-free and non-functional sGC heterodimer ( Dai et al, 2019 ). It is well established that oxidative stress, which plays a major role in the development of pulmonary vascular remodeling and a consequent increase of pulmonary pressure, can cause the oxidation of the sGC heme resulting in desensitization to NO signaling ( Shah et al, 2018 ). NO stimulates the insertion of heme in apo-sGC-β1, the dissociation of Hsp90 from the complex, and the association of sGC-α1 to form the active enzyme ( Ghosh et al, 2014 ).…”

Section: Heat Shock Protein 90 In Pulmonary Arterial Hypertensionmentioning

confidence: 99%

New Insights Into Heat Shock Protein 90 in the Pathogenesis of Pulmonary Arterial Hypertension

Zhao

Liu

et al. 2020

Front. Physiol.

View full text Add to dashboard Cite

Pulmonary arterial hypertension (PAH) is a multifactorial and progressive disorder. This disease is characterized by vasoconstriction and vascular remodeling, which results in increased pulmonary artery pressure and pulmonary vascular resistance. Although extensive studies have been carried out to understand the etiology, it is still unclear what intracellular factors contribute and integrate these pathological features. Heat shock protein 90 (Hsp90), a ubiquitous and essential molecular chaperone, is involved in the maturation of many proteins. An increasing number of studies have revealed direct connections between abnormal Hsp90 expression and cellular factors related to PAH, such as soluble guanylate cyclase and AMP-activated protein kinase. These studies suggest that the Hsp90 regulatory network is a major predictor of poor outcomes, providing novel insights into the pathogenesis of PAH. For the first time, this review summarizes the interplay between the Hsp90 dysregulation and different proteins involved in PAH development, shedding novel insights into the intrinsic pathogenesis and potentially novel therapeutic strategies for this devastating disease.

show abstract

Redox regulation of soluble guanylyl cyclase

Cited by 49 publications

References 105 publications

Stimulation of soluble guanylate cyclase improves donor organ function in rat heart transplantation

Stimulation of soluble guanylate cyclase improves donor organ function in rat heart transplantation

cGMP: a unique 2nd messenger molecule – recent developments in cGMP research and development

New Insights Into Heat Shock Protein 90 in the Pathogenesis of Pulmonary Arterial Hypertension

Contact Info

Product

Resources

About